Cardiovascular Diseases Commons^™

Phds/Cpt1b/Vdac1 Axis Regulates Long-Chain Fatty Acid Oxidation In Cardiomyocytes, Aude Angelini, Pradip K Saha, Antrix Jain, Sung Yun Jung, Randall L Mynatt, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported in ischemic or late-stage failing hearts. The mechanism regulating this metabolic switch remains poorly understood. Here, we report that loss of PHD2/3, the cellular oxygen sensors, blocks LCFA mitochondria uptake and β-oxidation in cardiomyocytes. In high-fat-fed mice, PHD2/3 deficiency improves glucose metabolism but exacerbates the cardiac defects. Mechanistically, we find that PHD2/3 bind to CPT1B, a key enzyme of mitochondrial LCFA uptake, promoting CPT1B-P295 hydroxylation. Further, we …

Cellular Regeneration As A Potential Strategy To Treat Cardiac Conduction Disorders, Satadru K Lahiri, Mohit M Hulsurkar, Xander Ht Wehrens

Faculty, Staff and Students Publications

Loss of atrioventricular conduction system (AVCS) cells due to either inherited or acquired deficits leads to conduction diseases, which can deteriorate into fatal cardiac arrhythmias and sudden death. In this issue of the JCI, Wang et al. constructed a mouse model of atrioventricular block (AVB) by inducing AVCS cell-specific injury using the Cx30.2 enhancer to drive expression of diphtheria toxin fragment A. AVCS cell ablation in adult mice led to irreversible AVB. jkjkIn contrast, AVCS cell injury in neonatal mice was followed by spontaneous recovery in a subset of mice, revealing a limited postnatal time window during which the regeneration …

Ucp3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin Ii-Induced Hypertension, Xu Chen, Sadia Ashraf, Nadia Ashraf, Romain Harmancey

Faculty, Staff and Student Publications

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3

Beta-Blockers In The Critically Ill: Friend Or Foe?, Mourad H Senussi

Faculty, Staff and Students Publications

No abstract provided.

Endothelium-Specific Depletion Of Lrp1 Improves Glucose Homeostasis Through Inducing Osteocalcin, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Cristian Coarfa, Kimal Rajapakshe, Dimuthu Perera, Jizhong Cheng, Huaizhu Wu, Christie M Ballantyne, Zheng Sun, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density …

Sudden Cardiac Death In Athletes, Darren C Tsang, Mark S Link

The Texas Heart Institute Journal

No abstract provided.

Avoidance Of St-Segment-Elevation Myocardial Infarction Treatment For >1 Week Due To Covid-19 Fears, Rahul V Annabathula, Gregory J Sinner, Talal S Alnabelsi, Rachel P Goodwin, Vincent L Sorrell

The Texas Heart Institute Journal

During the coronavirus disease 2019 (COVID-19) pandemic, social distancing guidelines have negatively affected the care-seeking behavior of patients with chronic medical conditions, including those with cardiovascular disease. We report the case of a 60-year-old man with vague gastrointestinal symptoms who waited more than 1 week to seek treatment for fear of COVID-19 infection. On presentation at another hospital, he was found to have had an anterior myocardial infarction, and he underwent percutaneous coronary intervention to stent an occluded proximal left anterior descending coronary artery. Subsequently, the patient experienced refractory cardiogenic shock and, during his transfer to our hospital, refractory ventricular …

Cheyne-Stokes Respiration In A 17-Year-Old Boy Awaiting Heart Transplantation, Nooralam A Rai, Aliva De, Carin Lamm

The Texas Heart Institute Journal

Cheyne-Stokes respiration is a pattern of alternating central apnea and hyperpnea. It is well described in adults with congestive heart failure, but not in children.

We report the case of a 17-year-old boy whose systolic heart failure was complicated by Cheyne-Stokes respiration. He was given supportive therapy until heart transplant, after which his Cheyne-Stokes respiration clinically resolved. Clinicians should be aware of this uncommon condition in pediatric and adolescent patients who have advanced heart failure and irregular breathing.

Medical And Device Therapy For Stroke Prevention In Patients With Atrial Fibrillation, Sophia Huang, Payam Safavi-Naeini, Abdi Rasekh

The Texas Heart Institute Journal

No abstract provided.

Hemodynamic Outcomes After Valve-In-Valve Transcatheter Aortic Valve Replacement: A Single-Center Experience, R Yazan Kherallah, Srikanth Koneru, Zvonimir Krajcer, Ourania Preventza, Kathryn G Dougherty, Melissa L Mccormack, Briana T Costello, Stephanie Coulter, Neil E Strickman, Juan Carlos Plana Gomez, Ali Mortazavi, Jose G Díez, James J Livesay, Joseph S Coselli, Guilherme V Silva

Faculty, Staff and Students Publications

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis.

METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and …

Continuous-Flow Left Ventricular Assist Device Support In Patients With Ischemic Versus Nonischemic Cardiomyopathy, Brendan P Chou, Andre Critsinelis, Harveen K Lamba, Gregory Long, Andrew B Civitello, Reynolds M Delgado, Subhasis Chatterjee

Faculty, Staff and Students Publications

To determine whether the cause of cardiomyopathy affects outcomes in patients who undergo continuous-flow left ventricular assist device support, we compared postimplant adverse events and survival between patients with ischemic and nonischemic cardiomyopathy. The inclusion criteria for the ischemic group were a history of myocardial infarction or revascularization (coronary artery bypass grafting or percutaneous coronary intervention), ≥75% stenosis of the left main or proximal left anterior descending coronary artery, or ≥75% stenosis of ≥2 epicardial vessels. From November 2003 through March 2016, 526 patients underwent device support: 256 (48.7%) in the ischemic group and 270 (51.3%) in the nonischemic group. …

Transcatheter Pulmonic Valve Implantation In Adult Patients With Prior Congenital Heart Surgery, Zachary A Spigel, Iki Adachi, Ziyad M Binsalamah, Dhaval Parekh, Athar M Qureshi

Faculty, Staff and Students Publications

BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) is now an established modality for pulmonary valve replacement in suitable candidates. We aim to describe our experience with TPVR in adults.

METHODS: This is a descriptive study of all TPVR performed in adults with congenital heart disease at a single institution from 2010-2020. All adult patients (defined as 18 years old or older at TPVR) were included. Time-to-event outcomes were described using Kaplan-Meier estimates with 95% confidence intervals (CIs).

RESULTS: Out of a total of 200 patients that had undergone TPVR, 81 patients (57% male) met the inclusion criteria, with a median age …

Cd11c Participates In Triggering Acute Graft-Versus-Host Disease During Bone Marrow Transplantation, Qianqian Wang, Xiuhua Su, Yi He, Mei Wang, Donglin Yang, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Aiming Pang, Yong Huang, Sizhou Feng, Christie M Ballantyne, Huaizhu Wu, Xiaolei Pei, Xiaoming Feng, Mingzhe Han, Erlie Jiang

Faculty, Staff and Students Publications

CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell‐derived DCs (MoDCs) inhibited the proliferation of CD4+ T cells and the differentiation into IFN‐γ‐producing T helper 1 (Th1) cells, which were critical in acute graft‐versus‐host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo‐BMT) murine models, we consistently found that CD11c‐deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN‐γ‐expressing CD4+ Th1 cells and CD8+ T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen …

A Simplified Approach To Identification Of Risk Status In Patients With Atherosclerotic Cardiovascular Disease, Aparna Sajja, Hsin-Fang Li, Kateri J Spinelli, Amir Ali, Salim S Virani, Seth S Martin, Ty J Gluckman

Faculty, Staff and Students Publications

OBJECTIVE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) Blood Cholesterol Guideline recommendation to classify patients with atherosclerotic cardiovascular disease (ASCVD) as very high-risk (VHR) vs not-VHR (NVHR) has important implications for escalation of medical therapy. We aimed to define the prevalence and clinical characteristics of these two groups within a large multi-state healthcare system and develop a simpler means to assist clinicians in identifying VHR patients using classification and regression tree (CART) analysis.

METHODS: We performed a retrospective analysis of all patients in a 28-hospital US healthcare system in 2018. ICD-10 codes were used to define the ASCVD …

The Design And Rationale Of A Multicenter Real-World Trial: The Southeastern Collaboration To Improve Blood Pressure Control In The Us Black Belt – Addressing The Triple Threat, Tina O Findley, Hope Northrup

Faculty, Staff and Student Publications

The incidence of congenital heart defect (CHD) has increased over the past fifty years, partly attributed to routine fetal anatomical examination by sonography during obstetric care and improvements in ultrasound technology and technique. Fetal findings on ultrasound in addition to maternal biomarkers are the backbone of first- and second-trimester screening for common genetic conditions, namely aneuploidy. Since the introduction of non-invasive prenatal testing (NIPT) using next-generation sequencing to sequence cell-free fetal DNA, the detection rate of common trisomies as well as sex chromosomal aneuploidies have markedly increased. As the use of NIPT continues to broaden, the best means of incorporating …

Rare Silent Ischemic Ventricular Septal Aneurysm And Rupture: A Multimodality Diagnostic Approach, Hong Loan Nguyen, Nicolas Palaskas, Nasser Lakkis, Rashed Tabbaa

Faculty, Staff and Students Publications

A multimodality approach in addition to high level of clinical suspicion and thorough physical examination is important in the diagnosis and management of left ventricular aneurysm and rupture after a silent inferior infarction.

The Cgas–Sting Pathway In Diabetic Retinopathy And Age-Related Macular Degeneration, Shannon Erhardt, Mingjie Zheng, Xiaolei Zhao, Tram P Le, Tina O Findley, Jun Wang

Faculty, Staff and Student Publications

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to the pharyngeal arch arteries, the developing cardiac outflow tract (OFT), cardiac valves, and interventricular septum. Various signaling pathways are shown to orchestrate the proper migration, compaction, and differentiation of cardiac NCCs during cardiovascular development. Any loss or dysregulation of signaling pathways in cardiac NCCs can lead to abnormal cardiovascular development during embryogenesis, resulting in abnormalities categorized as …

Modes Of Failure With Fractional Flow Reserve Guidewires: Insights From The Manufacturer And User Facility Device Experience Database, Nauman Khalid, Yagya Pandey, Umair Khalid, Hassan Kamran, Jason P Wermers, Lovely Chhabra, Mahboob Alam, Hani Jneid, Waleed Tallat Kayani

Faculty, Staff and Students Publications

BACKGROUND: Fractional flow reserve (FFR) measurement is commonly used in the cardiac catheterization laboratory to assess the functional significance of coronary arterial plaques. Robust real-world data on complications and modes of failure of FFR guidewires are limited.

AIM: To characterize these outcomes by analyzing the post-marketing surveillance data from the United States Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database for commonly used FFR guidewires.

METHODS: The MAUDE database was queried from January 2010 through April 2020 for 3 FFR guidewires [PressureWire

RESULTS: Guidewire tip fracture was the most commonly reported mode of failure, in 174 …

Highlights From Studies Presented At The Virtual American College Of Cardiology Scientific Sessions 2021: Staying Updated With The Latest Advancements In Prevention, Vardhmaan Jain, Mahmoud Al Rifai, Dhruv Mahtta, Jing Liu, Aliza Hussain, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: This review highlights late-breaking science presented at the Virtual American College of Cardiology Scientific Sessions 2021 that demonstrated advancements in preventative cardiology and introduced novel therapeutic modalities for the management of chronic kidney disease, heart failure, and COVID-19.

RECENT FINDINGS: The studies reviewed include clinical trials that assessed the use of dapagliflozin in patients with respiratory failure due to COVID-19 (DARE-19 trial); evinacumab for patients with severe hypertriglyceridemia and pancreatitis; effect of genotype-guided oral P2y12 inhibitors vs conventional clopidogrel on long-term ischemic outcomes after percutaneous coronary intervention (TAILOR-PCI trial); anticoagulation in patients hospitalized with COVID-19 (ACTION trial); …

Venovenous Extracorporeal Membrane Oxygenation To Facilitate Removal Of Endobronchial Tumors, Bryan Miles, Lucian A Durham, Jonathan Kurman, Lyle D Joyce, David W Johnstone, David Joyce, Paul J Pearson

The Texas Heart Institute Journal

Short-term extracorporeal membrane oxygenation is a useful adjunct to thoracic procedures. We report the cases of 2 middle-aged men who were supported with venovenous extracorporeal membrane oxygenation to facilitate tumor debulking and recanalization of the carina and mainstem bronchi. Neither patient had major complications or adverse events. These cases suggest that short-term extracorporeal membrane oxygenation is safe in patients undergoing complex resection or debulking of endobronchial lesions.

Sex-Related Disparities In Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease, Michelle T Lee, Dhruv Mahtta, David J Ramsey, Jing Liu, Arunima Misra, Khurram Nasir, Zainab Samad, Dipti Itchhaporia, Safi U Khan, Richard S Schofield, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There is a paucity of data regarding secondary prevention care disparities in women with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD), defined as an ASCVD event at 55 years or younger and 40 years or younger, respectively.

OBJECTIVE: To evaluate sex-based differences in antiplatelet agents, any statin, high-intensity statin (HIS) therapy, and statin adherence in patients with premature and extremely premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, multicenter, nationwide VA health care system-based study with patients enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. The study assessed patients who had at least 1 primary …

High Burden Of Subclinical And Cardiovascular Disease Risk In Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk In Communities (Aric) Study, Yvonne Commodore-Mensah, Mariana Lazo, Olive Tang, Justin B Echouffo-Tcheugui, Chiadi E Ndumele, Vijay Nambi, Dan Wang, Christie Ballantyne, Elizabeth Selvin

Faculty, Staff and Students Publications

OBJECTIVE: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

RESEARCH DESIGN AND METHODS: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, …

Delayed Treatment Of Acute Myocardial Infarction With Ventricular Septal Rupture Due To Patient Fear During The Covid-19 Pandemic, Minar Chhetry, Reema Bhatt, Nathan H Tehrani, Dimitrios V Avgerinos, Charles A Mack, Samuel J Lang, Xuming Dai

The Texas Heart Institute Journal

During the coronavirus disease 2019 (COVID-19) pandmic, more patients are presenting with complications late after acute myocardial infarction. We report the case of a 71-year-old man who delayed seeking medical care for 2 weeks, despite progressive shortness of breath, cough, and tactile fever, for fear of contracting COVID-19 in the hospital. Clinical and echocardiographic evaluation revealed a ventricular septal rupture secondary to acute myocardial infarction. The patient underwent urgent cardiac catheterization, followed by successful saphenous vein grafting to the left anterior descending coronary artery and open surgical repair of the ventricular septal rupture with a bovine pericardial patch. This case …

Sustained Use Of The Impella 50 Heart Pump Enables Bridge To Clinical Decisions In 34 Patients, Daniel W Nelson, Sakthi Sundararajan, Evan Klein, Lyle D Joyce, Lucian A Durham, David L Joyce, Asim A Mohammed

The Texas Heart Institute Journal

We studied whether sustained hemodynamic support (>7 d) with the Impella 5.0 heart pump can be used as a bridge to clinical decisions in patients who present with cardiogenic shock, and whether such support can improve their outcomes. We retrospectively reviewed cases of patients who had Impella 5.0 support at our hospital from August 2017 through May 2019. Thirty-four patients (23 with cardiogenic shock and 11 with severely decompensated heart failure) underwent sustained support for a mean duration of 11.7 ± 9.3 days (range, ≤48 d). Of 29 patients (85.3%) who survived to next therapy, 15 were weaned from …

A Review Of The Cardiac And Cardiovascular Effects Of Covid-19 In Adults And Children, Bibhuti B Das, S Kristen Sexon Tejtel, Shriprasad Deshpande, Lara S Shekerdemian

The Texas Heart Institute Journal

Symptomatic coronavirus disease 2019 (COVID-19) typically affects the respiratory system but can involve the cardiovascular system. Cardiac complications of COVID-19 can result directly from myocarditis or indirectly from numerous other mechanisms. Differentiating between primary and secondary cardiovascular involvement-our focus in this review-may help to identify the long-term effects of COVID-19 on the heart in adults and children.

Cardiovascular Outcomes In Patients With Mitochondrial Disease In The United States: A Propensity Score Analysis, Tran Nguyen, Talal Alzahrani, Joseph Krepp, Gurusher Panjrath

The Texas Heart Institute Journal

Mitochondrial disease comprises a wide range of genetic disorders caused by mitochondrial dysfunction. Its rarity, however, has limited the ability to assess its effects on clinical outcomes. To evaluate this relationship, we collected data from the 2016 National Inpatient Sample, which includes data from >7 million hospital stays. We identified 705 patients (mean age, 22 ± 20.7 yr; 54.2% female; 67.4% white) whose records included the ICD-10-CM code E88.4. We also identified a propensity-matched cohort of 705 patients without mitochondrial disease to examine the effect of mitochondrial disease on major adverse cardiovascular events, including all-cause in-hospital death, cardiac arrest, and …

Nlrp3 Inflammasome Is A Key Driver Of Obesity-Induced Atrial Arrhythmias, Larry Scott, Anke C Fender, Arnela Saljic, Luge Li, Xiaohui Chen, Xiaolei Wang, Dominik Linz, Jilu Lang, Mathias Hohl, Darragh Twomey, Thuy T Pham, Rodrigo Diaz-Lankenau, Mihail G Chelu, Markus Kamler, Mark L Entman, George E Taffet, Prashanthan Sanders, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

AIMS: Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF.

METHODS AND RESULTS: Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in …

Development And Validation Of Machine Learning-Based Race-Specific Models To Predict 10-Year Risk Of Heart Failure: A Multicohort Analysis, Matthew W Segar, Byron C Jaeger, Kershaw V Patel, Vijay Nambi, Chiadi E Ndumele, Adolfo Correa, Javed Butler, Alvin Chandra, Colby Ayers, Shreya Rao, Alana A Lewis, Laura M Raffield, Carlos J Rodriguez, Erin D Michos, Christie M Ballantyne, Michael E Hall, Robert J Mentz, James A De Lemos, Ambarish Pandey

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races.

METHODS: We performed a retrospective analysis of 4 large, community cohort studies (ARIC [Atherosclerosis Risk in Communities], DHS [Dallas Heart Study], JHS [Jackson Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) with adjudicated HF events. …

Arteriovenous Fistula Formation After Transradial Coronary Intervention, Khader Herzallah, Abdulmohsin Ahmadjee, Yehia Saleh, George S Abela

The Texas Heart Institute Journal

No abstract provided.

Continuous-Flow Left Ventricular Assist Device Explantation After More Than 5 Years Of Circulatory Support And Ventricular Reconditioning, George V Letsou, Andrew C W Baldwin, Andrew B Civitello, William E Cohn, O H Frazier

The Texas Heart Institute Journal

Continuous-flow left ventricular assist devices have proved to be effective, durable, life-saving tools in patients with end-stage heart failure. However, because of the risks associated with mechanical circulatory support (including stroke, infection, gastrointestinal bleeding, and device malfunction), the optimal goal of device therapy is myocardial recovery and device removal. Ventricular reconditioning and pump explantation after continuous-flow support have been reported; however, little is known about variables that govern the pace and degree of myocardial response in patients who experience such recovery. We describe our long-term pump-weaning strategy for a 25-year-old man who had a continuous-flow device implanted and then needed …