Jason D Roberts, S Yukiko Asaki, Andrea Mazzanti, J Martijn Bos, Izabela Tuleta, Alison R Muir, Lia Crotti, Andrew D Krahn, Valentina Kutyifa, M Benjamin Shoemaker, Christopher L Johnsrude, Takeshi Aiba, Luciana Marcondes, Anwar Baban, Sharmila Udupa, Brynn Dechert, Peter Fischbach, Linda M Knight, Eric Vittinghoff, Deni Kukavica, Birgit Stallmeyer, John R Giudicessi, Carla Spazzolini, Keiko Shimamoto, Rafik Tadros, Julia Cadrin-Tourigny, Henry J Duff, Christopher S Simpson, Thomas M Roston, Yanushi D Wijeyeratne, Imane El Hajjaji, Maisoon D Yousif, Lorne J Gula, Peter Leong-Sit, Nikhil Chavali, Andrew P Landstrom, Gregory M Marcus, Sven Dittmann, Arthur A M Wilde, Elijah R Behr, Jacob Tfelt-Hansen, Melvin M Scheinman, Marco V Perez, Juan Pablo Kaski, Robert M Gow, Fabrizio Drago, Peter F Aziz, Dominic J Abrams, Michael H Gollob, Jonathan R Skinner, Wataru Shimizu, Elizabeth S Kaufman, Dan M Roden, Wojciech Zareba, Peter J Schwartz, Eric Schulze-Bahr, Susan P Etheridge, Silvia G Priori, Michael J Ackerman
Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multi-center collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (JLNS2, N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries...
January 16, 2020: Circulation
María Trinidad Soria-Florido, Olga Castañer, Camille Lassale, Ramon Estruch, Jordi Salas-Salvadó, Miguel Ángel Martínez-González, Dolores Corella, Emilio Ros, Fernando Arós, Roberto Elosua, José Lapetra, Miquel Fiol, Angel Alonso-Gómez, Enrique Gómez-Gracia, Lluís Serra-Majem, Xavier Pintó, Mònica Bulló, Miguel Ruiz-Canela, Jose V Sorlí, Álvaro Hernáez, Montserrat Fitó
Background: Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that HDL atheroprotective role lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been comprehensively investigated. Methods: We conducted a case-control study nested within the PREDIMED ( Prevención con Dieta Mediterránea ) cohort, originally a randomized trial where participants followed a Mediterranean or low-fat diet...
January 16, 2020: Circulation
Zhiyong Zou, Karly Cini, Bin Dong, Yinghua Ma, Jun Ma, David P Burgner, George C Patton
Background: Brazil, Russia, India, China and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS, and associations with age, period and birth cohort. Methods: Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992- 2016. Period was defined as survey year, and period effects reflect population wide exposure at a circumscribed point in time...
January 16, 2020: Circulation
Gopalkrishna Sreejit, Ahmed Abdel-Latif, Baskaran Athmanathan, Rahul Annabathula, Ashish Dhyani, Sunil K Noothi, Gregory A Quaife-Ryan, Annas Al-Sharea, Gerard Pernes, Dragana Dragoljevic, Hind Lal, Kate Schroder, Beatriz Y Hanaoka, Chander Raman, Maria B Grant, James E Hudson, Susan Smyth, Enzo R Porrello, Andrew J Murphy, Prabhakara R Nagareddy
Background: Myocardial infarction (MI) triggers myelopoiesis resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear. Methods: Using a mouse model of the permanent ligation of the left anterior descending (LAD) artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of acute inflammatory response and the underlying signaling pathways...
January 16, 2020: Circulation
Jesse A Columbo, Robert M Zwolak, Edward J Arous, Philip P Goodney, Michael P Lilly, H Gilbert Welch
Background: Individuals with carotid stenosis enter surveillance or are considered for surgery based upon disease severity assessed by ultrasound. However, there is variation in the ultrasound diagnostic thresholds used to determine disease severity. Our objective was to describe this variation and its potential impact on patients. Methods: To describe the variation in carotid ultrasound diagnostic thresholds, we examined testing protocols from 338 accredited vascular testing centers in the United States. To determine the potential impact of this variation, we applied the range of thresholds to carotid ultrasound parameters from two groups: a population-based sample age ≥65 years in the Cardiovascular Health Study (n=4,791), and a cohort of patients who underwent surgery for asymptomatic carotid stenosis in the Vascular Quality Initiative registry (n=28,483)...
January 16, 2020: Circulation
Matthew A Caporizzo, Christina Yingxian Chen, Ken Bedi, Kenneth B Margulies, Benjamin L Prosser
Background: Diastolic dysfunction is a prevalent and therapeutically intractable feature of heart failure (HF). Increasing ventricular compliance can improve diastolic performance, but the viscoelastic forces that resist diastolic filling and become elevated in human HF are poorly defined. Having recently identified post-translationally detyrosinated microtubules as a source of viscoelasticity in cardiomyocytes, we sought to test whether microtubules contribute meaningful viscoelastic resistance to diastolic stretch in human myocardium...
January 16, 2020: Circulation
Jorge Carvalho, Ramesh Chennupati, Rui Li, Stefan Günther, Harmandeep Kaur, Wencai Zhao, Sarah Tonack, Michael Kurz, Nadja Mößlein, Moritz Bünemann, Stefan Offermanns, Nina Wettschureck
Background: G-protein-coupled receptors (GPCRs) are important regulators of contractility and differentiation in vascular smooth muscle cells (SMC), but the specific function of SMC-expressed orphan GPCR GPRC5B is unclear. Methods: We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMC in vitro as well as in tamoxifen-inducible, SMC-specific knockout mice (iSM-Gprc5b-KO) under conditions of arterial hypertension and atherosclerosis in vivo. Results: Mesenteric arteries from SMC-specific Gprc5b-KOs showed ex vivo significantly enhanced prostacyclin receptor (IP)-dependent relaxation, whereas responses to other relaxant or contractile factors were normal...
January 16, 2020: Circulation
Mohamud R Daya, Brian G Leroux, Paul Dorian, Thomas D Rea, Craig D Newgard, Laurie J Morrison, Joshua R Lupton, James J Menegazzi, Joseph P Ornato, George Sopko, Jim Christenson, Ahamed Idris, Purav Mody, Gary M Vilke, Caroline Herdeman, David Barbic, Peter J Kudenchuk
Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest (OHCA) from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/VT). How this might be influenced by the route of drug administration is not known. Methods: In this pre-specified analysis of a randomized, placebo-controlled clinical trial, we compared differences in survival to hospital discharge in adults with shock-refractory VF/VT OHCA who were randomized by emergency medical services (EMS) personnel to an antiarrhythmic drug versus placebo in the Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study (ALPS), when stratified by the intravenous (IV) versus intraosseous (IO) route of administration...
January 16, 2020: Circulation
Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Tomokazu Murakawa, Jumpei Ito, Yohei Tanada, Kazuhiko Nishida, Osamu Yamaguchi, Takashi Satoh, Ajay M Shah, Shizuo Akira, Kinya Otsu
Background: Proinflammatory cytokines play an important role in the pathogenesis of heart failure. However, the mechanisms responsible for maintaining sterile inflammation within failing hearts remain poorly defined. Although transcriptional control is important for proinflammatory cytokine gene expression, the stability of the mRNA also contributes to the kinetics of immune responses. Regnase-1 is an RNase involved in the degradation of a set of proinflammatory cytokine mRNAs in immune cells. The role of Regnase-1 in non-immune cells such as cardiomyocytes remains to be elucidated...
January 14, 2020: Circulation
Alana A Lewis, Colby R Ayers, Elizabeth Selvin, Ian Neeland, Christie Ballantyne, Vijay Nambi, Ambarish Pandey, Tiffany M Powell-Wiley, Mark H Drazner, Mercedes R Carnethon, Jarett D Berry, Stephen L Seliger, Christopher R deFilippi, James A de Lemos
Background: A "malignant" subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk. Methods: Participants (n=15, 710) without prevalent cardiovascular disease were pooled from three population-based cohort studies, the Atherosclerosis Risk in Communities Study (ARIC), the Dallas Heart Study (DHS), and the Multi-Ethnic Study of Atherosclerosis (MESA)...
January 14, 2020: Circulation
Nithya Neelakantan, Jowy Yi Hoong Seah, Rob M van Dam
Background: Coconut oil is high in saturated fat and may, therefore, raise serum cholesterol concentrations, but beneficial effects on other cardiovascular risk factors have also been suggested. Therefore, we conducted a systematic review of the effect of coconut oil consumption on blood lipids and other cardiovascular risk factors compared with other cooking oils using data from clinical trials. Methods: We searched PubMed, SCOPUS, Cochrane Registry, and Web of Science through June 2019. We selected trials that compared the effects of coconut oil consumption with other fats that lasted at least 2 weeks...
January 13, 2020: Circulation
Frank M Sacks
No abstract text is available yet for this article.
January 13, 2020: Circulation
Lu Gan, Dina Xie, Jing Liu, Wayne Bond Lau, Theodore A Christopher, Bernard Lopez, Ling Zhang, Erhe Gao, Walter Koch, Xin-Liang Ma, Yajing Wang
Background: Diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury by incompletely understood mechanisms. Adipocyte dysfunction contributes to remote organ injury. However, the molecular mechanisms linking dysfunctional adipocytes to increased MI/R injury remain unidentified. The current study attempted to clarify whether and how small extracellular vesicles (sEV) may mediate pathological communication between diabetic adipocytes and cardiomyocytes, exacerbating MI/R injury. Methods: Adult male mice were fed a normal or a high fat diet for 12 weeks...
January 10, 2020: Circulation
Veena S Rao, Jeffrey M Turner, Matthew Griffin, Devin Mahoney, Jennifer Asher, Sangchoon Jeon, Peter S Yoo, Nabil Boutagy, Attila Feher, Albert Sinusas, F Perry Wilson, Fredric Finkelstein, Jeffrey M Testani
Background: Loop diuretics have well described toxicities and loss of response to these agents is common. Alternative strategies are needed for the maintenance of euvolemia in heart failure (HF). Non-renal removal of sodium directly across the peritoneal membrane (direct sodium removal, DSR) using a sodium free osmotic solution should result in extraction of large quantities of sodium with limited off target solute removal. Methods: This report describes the pre-clinical development and first-in-human proof of concept for DSR...
January 8, 2020: Circulation
D Ian Paterson, George Wells, Fernanda Erthal, Lisa Mielniczuk, Eileen O'Meara, James White, Kim A Connelly, Juhani Knuuti, Miroslaw Rajda, Mika Laine, Benjamin J W Chow, Riina Kandolin, Li Chen, Alexander Dick, Carole Dennie, Linda Garrard, Justin Ezekowitz, Rob Beanlands, Kwan-Leung Chan
Background: Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF), however there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Hypothesis: Routine use of CMR will yield more specific diagnoses in non-ischemic HF. Secondary hypothesis: Routine use of CMR will improve patient outcomes. Methods: Patients with non-ischemic HF were randomized to Routine versus Selective CMR. Patients in the Routine strategy underwent echo and CMR whereas those assigned to Selective use underwent echo with or without CMR according to the clinical presentation...
January 8, 2020: Circulation
Fiona Bartoli, Marc A Bailey, Baptiste Rode, Philippe Mateo, Fabrice Antigny, Kaveen Bedouet, Pascale Gerbaud, Rajendra Gosain, Jeffrey Plante, Katherine Norman, Susana Gomez, Florence Lefebvre, Catherine Rucker-Martin, Justin F X Ainscough, Mark T Kearney, Alexander-Francisco Bruns, Jian Shi, Hollie L Appleby, Richard S Young, Heba M Shawer, Marjolaine Debant, Ana-Maria Gomez, David J Beech, Richard Foster, Jean-Pierre Benitah, Jessica Sabourin
Background: Orai1 is a critical ion channel subunit, best recognized as a mediator of storeoperated Ca2+ entry (SOCE) in non-excitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. Methods: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop JPIII, a small-molecule Orai1 channel inhibitor suitable for in vivo delivery...
January 7, 2020: Circulation
Robb D Kociol, Leslie T Cooper, James C Fang, Javid J Moslehi, Peter S Pang, Marwa A Sabe, Ravi V Shah, Daniel B Sims, Gaetano Thiene, Orly Vardeny
Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care...
January 6, 2020: Circulation
Xin Tang, Lihong Pan, Shuang Zhao, Feiyue Dai, Menglin Chao, Hong Jiang, Xuesong Li, Zhe Lin, Zhengrong Huang, Guoliang Meng, Chun Wang, Chan Chen, Jin Liu, Xin Wang, Albert Ferro, Hong Wang, Hongshan Chen, Yuanqing Gao, Qiulun Lu, Liping Xie, Yi Han, Yong Ji
Background: S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of cardiovascular disease. The aim of this study was to determine the role of S-nitrosylation of muscle LIM protein (MLP) in myocardial hypertrophy, as well as the mechanism by which SNO-MLP modulates hypertrophic growth in response to pressure overload. Methods: Myocardial samples from patients and animal models exhibiting myocardial hypertrophy were examined for SNO-MLP level using biotin-switch methods...
January 6, 2020: Circulation
Claire E Raphael, Véronique L Roger, Yader Sandoval, Mandeep Singh, Malcolm Bell, Amir Lerman, Charanjit S Rihal, Bernard J Gersh, Bradley Lewis, Ryan J Lennon, Allan S Jaffe, Rajiv Gulati
Background: Type 2 myocardial infarction (T2MI) occurs due to an acute imbalance in myocardial oxygen supply and demand in the absence of athero-thrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown and the long-term outcomes incompletely characterized. Methods: We prospectively recruited residents of Olmsted County, Minnesota who experienced an event associated with a cardiac troponin T (cTnT) >99th percentile of a normal reference population (≥0...
January 6, 2020: Circulation
Kasper Andersen, Ulf Hållmarker, Stefan James, Johan Sundström
Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet ...
January 6, 2020: Circulation
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