Omar Niss1, Charles T Quinn2, Adam Lane3, Joshua Daily4, Philip R Khoury4, Nihal Bakeer2, Thomas R Kimball4, Jeffrey A Towbin4, Punam Malik5, Michael D Taylor4. 1. Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: omar.niss@cchmc.org. 2. Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 4. Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 5. Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Abstract
OBJECTIVES: The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). BACKGROUND: Cardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. METHODS: In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. RESULTS: In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e') were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e' correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. CONCLUSIONS: Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.
OBJECTIVES: The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). BACKGROUND: Cardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. METHODS: In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. RESULTS: In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e') were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e' correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. CONCLUSIONS:Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.
Authors: Antoni Bayes-Genis; Rafael Vazquez; Teresa Puig; Carlos Fernandez-Palomeque; Jordi Fabregat; Alfredo Bardají; Domingo Pascual-Figal; Jordi Ordoñez-Llanos; Mariano Valdes; Albert Gabarrús; Ricardo Pavon; Luis Pastor; Jose Ramon Gonzalez Juanatey; Jesus Almendral; Miquel Fiol; Vicente Nieto; Carlos Macaya; Juan Cinca; Antoni Bayes de Luna Journal: Eur J Heart Fail Date: 2007-06-13 Impact factor: 15.534
Authors: Sherif F Nagueh; Christopher P Appleton; Thierry C Gillebert; Paolo N Marino; Jae K Oh; Otto A Smiseth; Alan D Waggoner; Frank A Flachskampf; Patricia A Pellikka; Arturo Evangelista Journal: J Am Soc Echocardiogr Date: 2009-02 Impact factor: 5.251
Authors: Courtney D Fitzhugh; Naudia Lauder; Jude C Jonassaint; Marilyn J Telen; Xiongce Zhao; Elizabeth C Wright; Francis R Gilliam; Laura M De Castro Journal: Am J Hematol Date: 2010-01 Impact factor: 10.047
Authors: Patrick T McGann; Omar Niss; Min Dong; Anu Marahatta; Thad A Howard; Tomoyuki Mizuno; Adam Lane; Theodosia A Kalfa; Punam Malik; Charles T Quinn; Russell E Ware; Alexander A Vinks Journal: Am J Hematol Date: 2019-06-12 Impact factor: 10.047
Authors: Bryan C Hambley; Rania Abdul Rahman; Maxwell Reback; Mary Ann O'Riordan; Nathan Langer; Robert C Gilkeson; Mahazarin Ginwalla; Jane A Little; Robert Schilz Journal: Haematologica Date: 2018-07-13 Impact factor: 9.941
Authors: Omar Niss; Robert Fleck; Fowe Makue; Tarek Alsaied; Payal Desai; Jeffrey A Towbin; Punam Malik; Michael D Taylor; Charles T Quinn Journal: Blood Date: 2017-05-15 Impact factor: 22.113
Authors: Charles T Quinn; Eric P Smith; Shahriar Arbabi; Paramjit K Khera; Christopher J Lindsell; Omar Niss; Clinton H Joiner; Robert S Franco; Robert M Cohen Journal: Am J Hematol Date: 2016-11-08 Impact factor: 10.047