title: Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy.
abstract: BACKGROUND
  Cardiac resynchronization therapy using bi-ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS-complex. In the absence of QRS prolongation, however, device-based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell-based approach in the setting of narrow QRS-complex HF.
  
  
  RESULTS
  Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of stress-triggered dilated cardiomyopathy. In contrast to rampant end-stage disease afflicting untreated cohorts, stem cell intervention early in disease, characterized by mechanical dyssynchrony and a narrow QRS-complex, aborted progressive dyssynchronous HF and prevented QRS widening. Stem cell-treated hearts acquired coordinated ventricular contraction and relaxation supporting systolic and diastolic performance. Rescue of contractile dynamics was underpinned by a halted left ventricular dilatation, limited hypertrophy, and reduced fibrosis. Reverse remodeling reflected a restored cardiomyopathic proteome, enforced at systems level through correction of the pathological molecular landscape and nullified adverse cardiac outcomes. Cell therapy of a dyssynchrony-prone cardiomyopathic cohort translated prospectively into improved exercise capacity and prolonged survivorship.
  
  
  CONCLUSIONS
  In narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device-autonomous resynchronization therapy for refractory disease.
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Satsuki
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: D Kent
authors.initials: DK
authors.lastname: Arrell
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Almudena
authors.initials: A
authors.lastname: Martinez-Fernandez
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Atta
authors.initials: A
authors.lastname: Behfar
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Garvan C
authors.initials: GC
authors.lastname: Kane
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.) Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN (C.M.P.T.).
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Perez-Terzic
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Crespo-Diaz
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McDonald
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Saranya P
authors.initials: SP
authors.lastname: Wyles
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Jelena
authors.initials: J
authors.lastname: Zlatkovic-Lindor
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.) Division of General Internal Medicine, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN (T.J.N.).
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000628:therapy; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005355:Fibrosis / Q000473:pathology; D006329:Heart Conduction System / Q000002:abnormalities / Q000503:physiopathology; D006333:Heart Failure / Q000517:prevention & control*; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D016896:Treatment Outcome; D020257:Ventricular Remodeling
keywords: mechanical discordance; proteome; resynchronization; speckle‐tracking; stem cells