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  1. Article: Atherosclerosis as a disease of failed endogenous repair.

    Zenovich, Andrey G / Taylor, Doris A

    Frontiers in bioscience : a journal and virtual library

    2008  Volume 13, Page(s) 3621–3636

    Abstract: As coronary artery disease (CAD) continues to be the primary cause of mortality, a more in-depth understanding of pathophysiology and novel treatments are being sought. The past two decades have established inflammation as a driving force behind CAD-- ... ...

    Abstract As coronary artery disease (CAD) continues to be the primary cause of mortality, a more in-depth understanding of pathophysiology and novel treatments are being sought. The past two decades have established inflammation as a driving force behind CAD--from endothelial dysfunction to heart failure. Recent advances in stem/progenitor cell biology have led to initial applications of progenitor cells in CAD continuum and have revealed that atherosclerosis is, at least in part, a disease of failed endogenous vascular repair. Several key progenitor cell populations including endothelial progenitor cells (AC133+/CD34+ population), vascular progenitors (CD31+/CD45(low) population), KDR+ cells and other bone marrow subtypes are mobilized for vascular repair. However, age and risk factors negatively impact these cells even prior to clinical CAD. Sex-based differences in progenitor cell capacity for repair have emerged as a new research focus that may offer mechanistic insights into clinical CAD discrepancies between men and women. Quantifying injury and cell-based repair and better defining their interactions should enable us to halt or even prevent CAD by enhancing the repair side of the repair/injury equation.
    MeSH term(s) Antigens, CD/physiology ; Atherosclerosis/complications ; Atherosclerosis/physiopathology ; Coronary Disease/epidemiology ; Fertility ; Humans ; Stem Cells/physiology ; Stroke/epidemiology ; Wound Healing
    Chemical Substances Antigens, CD
    Language English
    Publishing date 2008-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2141320-4
    ISSN 1093-9946
    ISSN 1093-9946
    DOI 10.2741/2954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cell therapy in kidney disease: cautious optimism... but optimism nonetheless.

    Zenovich, Andrey G / Taylor, Doris A

    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis

    2007  Volume 27 Suppl 2, Page(s) S94–103

    Abstract: The recently discovered therapeutic potential of stem or progenitor cells has initiated development of novel treatments in a number of diseases-treatments that could not only improve patients' quality of life, but also halt or even prevent disease ... ...

    Abstract The recently discovered therapeutic potential of stem or progenitor cells has initiated development of novel treatments in a number of diseases-treatments that could not only improve patients' quality of life, but also halt or even prevent disease progression. Hypertension; fluctuations in glycemia, electrolytes, nutrient levels, and circulating volume; and frequent infections and the associated inflammation all greatly impair the endothelium in patients undergoing peritoneal dialysis. As our understanding of the regulatory function of the endothelium advances, focus is increasingly being placed on endothelial repair in acute and chronic renal failure and after renal transplantation. The potential of progenitor cells to repair damaged endothelium and to reduce inflammation in patients with renal failure remains unexamined; however, a successful cell therapy could reduce morbidity and mortality in kidney disease. Important contributions have been made in identifying progenitor cell populations in the kidney, and further investigations into the relationships of these cells with the pathophysiology of the disease are underway. As the kidney disease field prepares for the first human trials of progenitor cell therapies, we deemed it important to review representative original research, and to share our perspectives and lessons learned from clinical trials of progenitor cell-based therapies that have commenced in patients with cardiovascular disease.
    MeSH term(s) Cardiovascular Diseases/etiology ; Cardiovascular Diseases/therapy ; Clinical Trials as Topic ; Disease Progression ; Epithelial Cells/physiology ; Humans ; Inflammation ; Kidney/cytology ; Kidney Transplantation ; Peritoneal Dialysis ; Quality of Life ; Renal Insufficiency/complications ; Renal Insufficiency/therapy ; Stem Cell Transplantation/methods ; Stem Cells/physiology
    Language English
    Publishing date 2007-06-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 645010-6
    ISSN 0896-8608
    ISSN 0896-8608
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Cell therapy for left ventricular remodeling.

    Taylor, Doris A / Zenovich, Andrey G

    Current heart failure reports

    2007  Volume 4, Issue 1, Page(s) 3–10

    Abstract: The increasing longevity of patients with heart failure (HF) and the rise in the incidence of HF has created an urgent need to effectively treat and prevent left ventricular remodeling. Within the past 6 years, skeletal myoblast and bone marrow ... ...

    Abstract The increasing longevity of patients with heart failure (HF) and the rise in the incidence of HF has created an urgent need to effectively treat and prevent left ventricular remodeling. Within the past 6 years, skeletal myoblast and bone marrow mononuclear cell transplantation have been undertaken in over 200 patients with HF, geared to the underlying injury, not just its mechanisms. Early safety/feasibility studies showed promising but somewhat conflicting secondary symptomatic and functional improvements, and safety concerns have arisen. However, the patient population, cell type, dose, time, mode of delivery, and outcome measures differed-making comparisons problematic. It is now time to: 1) create a central registry of all patients treated with cells; 2) perform side-by-side comparisons of different types of cells in patients with similar HF states; 3) agree on standardized trial designs; and 4) define acceptable and unacceptable outcomes (and measures) compared with both standard of care and to other emerging therapies. By doing so, we can avoid the pitfalls that previous biologics (eg, angiogenic gene therapy) have suffered, increase the likelihood of success, shorten the time-to-presentation of cell-based algorithms to clinicians, and deliver these therapies to patients who await new ways of reduction of symptoms and improvement of quality of life.
    MeSH term(s) Bone Marrow Transplantation ; Clinical Trials as Topic ; Heart Failure/physiopathology ; Heart Failure/surgery ; Heart Failure/therapy ; Humans ; Myoblasts, Skeletal/transplantation ; Research Design ; Stroke Volume ; Ventricular Remodeling
    Language English
    Publishing date 2007-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2151202-4
    ISSN 1546-9530
    ISSN 1546-9530
    DOI 10.1007/s11897-007-0019-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Identical twins with hypertrophic cardiomyopathy and apical aneurysm.

    Zenovich, Andrey G / Lesser, John R / Hanna, Connie A / Maron, Barry J

    The American journal of cardiology

    2006  Volume 97, Issue 7, Page(s) 1109

    Abstract: Left ventricular apical aneurysms, in absence of coronary artery disease, occur in approximately 1% of patients with hypertrophic cardiomyopathy (HC). Identical twins, age 44 years, are presented with HC and identical LV morphology, including apical ... ...

    Abstract Left ventricular apical aneurysms, in absence of coronary artery disease, occur in approximately 1% of patients with hypertrophic cardiomyopathy (HC). Identical twins, age 44 years, are presented with HC and identical LV morphology, including apical aneurysms. These cases demonstrate a genetic predisposition to the development of apical aneurysm, as well as overall LV morphology, in patients with HC.
    MeSH term(s) Adult ; Cardiomyopathy, Hypertrophic/complications ; Cardiomyopathy, Hypertrophic/pathology ; Cardiomyopathy, Hypertrophic/physiopathology ; Diseases in Twins ; Female ; Heart Aneurysm/complications ; Heart Aneurysm/pathology ; Heart Aneurysm/physiopathology ; Heart Ventricles ; Humans ; Twins, Monozygotic
    Language English
    Publishing date 2006-04-01
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 80014-4
    ISSN 1879-1913 ; 0002-9149
    ISSN (online) 1879-1913
    ISSN 0002-9149
    DOI 10.1016/j.amjcard.2005.10.059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Images in cardiovascular medicine. Hypertrophic cardiomyopathy with apical aneurysm.

    Zenovich, Andrey G / Lesser, John R / Casey, Susan A / Maron, Barry J

    Circulation

    2004  Volume 110, Issue 16, Page(s) e450

    MeSH term(s) Aged ; Cardiomyopathy, Hypertrophic/complications ; Contrast Media ; Coronary Aneurysm/etiology ; Gadolinium ; Humans ; Magnetic Resonance Imaging, Cine ; Male ; Middle Aged
    Chemical Substances Contrast Media ; Gadolinium (AU0V1LM3JT)
    Language English
    Publishing date 2004-10-19
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/01.CIR.0000145174.74063.C1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Death in a young athlete due to commotio cordis despite prompt external defibrillation.

    Maron, Barry J / Wentzel, David C / Zenovich, Andrey G / Estes, N A Mark / Link, Mark S

    Heart rhythm

    2005  Volume 2, Issue 9, Page(s) 991–993

    MeSH term(s) Adult ; Athletic Injuries/complications ; Cardiopulmonary Resuscitation ; Death, Sudden, Cardiac/etiology ; Defibrillators ; Echocardiography ; Electrocardiography ; Fatal Outcome ; Humans ; Male ; Thoracic Injuries/complications ; Treatment Failure ; Ventricular Fibrillation/diagnosis ; Ventricular Fibrillation/etiology ; Ventricular Fibrillation/therapy
    Language English
    Publishing date 2005-09
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2229357-7
    ISSN 1556-3871 ; 1547-5271
    ISSN (online) 1556-3871
    ISSN 1547-5271
    DOI 10.1016/j.hrthm.2005.06.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Relation of electrocardiographic patterns to phenotypic expression and clinical outcome in hypertrophic cardiomyopathy.

    Montgomery, Julia V / Harris, Kevin M / Casey, Susan A / Zenovich, Andrey G / Maron, Barry J

    The American journal of cardiology

    2005  Volume 96, Issue 2, Page(s) 270–275

    Abstract: Twelve-lead electrocardiography, a traditional component in evaluations of patients with hypertrophic cardiomyopathy (HC), is often regarded as a marker for the magnitude of left ventricular (LV) hypertrophy, which in turn has been linked to sudden death ...

    Abstract Twelve-lead electrocardiography, a traditional component in evaluations of patients with hypertrophic cardiomyopathy (HC), is often regarded as a marker for the magnitude of left ventricular (LV) hypertrophy, which in turn has been linked to sudden death risk. To determine whether electrocardiographic (ECG) patterns have clinical utility by accurately reflecting phenotypic expression or predicting clinical outcome, voltages and patterns were compared with LV wall thicknesses assessed by echocardiography and with clinical outcomes in 448 consecutive patients with HC. Significant but relatively weak correlations were evident between maximum LV wall thickness and ECG voltage: r = 0.295 (p <0.01) for the sum of R- and S-wave voltages in all 12 leads, r = 0.254 (p <0.01) for the maximum R or S wave in any lead, and r = 0.210 (p <0.01) for the sum of SV(1) (or SV(2)) and RV(5) (or RV(6)). Of 55 patients with extreme LV hypertrophy (LV wall thickness > or =30 mm), only 24 (44%) showed greatly increased ECG voltage > or =30 mm in any lead. Of 102 patients with outflow gradients > or =30 mm Hg at rest, only 43 (42%) had ECG voltage > or =30 mm in any lead. Normal ECG results were uncommonly associated with HC-related death (1 of 40 patients, 2.5%) but had similar prevalence in surviving patients (17 of 376 patients, 4.5%; p = NS). In conclusion, in HC, 12-lead ECG voltages are not a reliable clinical marker for the magnitude of LV hypertrophy or outflow obstruction. Diverse ECG patterns, consistent with heterogeneous expression of this disease, did not predict HC-related death. Scalar electrocardiography has selective but limited power in routine clinical assessments of patients with HC.
    MeSH term(s) Adult ; Aged ; Cardiomyopathy, Hypertrophic/diagnosis ; Cardiomyopathy, Hypertrophic/diagnostic imaging ; Cardiomyopathy, Hypertrophic/genetics ; Cardiomyopathy, Hypertrophic/mortality ; Cohort Studies ; Death, Sudden, Cardiac ; Echocardiography, Doppler ; Electrocardiography ; Female ; Gene Expression Regulation ; Humans ; Male ; Middle Aged ; Phenotype ; Probability ; Prognosis ; Retrospective Studies ; Risk Assessment ; Sensitivity and Specificity ; Severity of Illness Index ; Survival Analysis
    Language English
    Publishing date 2005-07-15
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 80014-4
    ISSN 1879-1913 ; 0002-9149
    ISSN (online) 1879-1913
    ISSN 0002-9149
    DOI 10.1016/j.amjcard.2005.03.058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy.

    Adabag, A Selcuk / Casey, Susan A / Kuskowski, Michael A / Zenovich, Andrey G / Maron, Barry J

    Journal of the American College of Cardiology

    2005  Volume 45, Issue 5, Page(s) 697–704

    Abstract: Objectives: The goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort.: Background: Hypertrophic cardiomyopathy is associated with arrhythmia-related ... ...

    Abstract Objectives: The goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort.
    Background: Hypertrophic cardiomyopathy is associated with arrhythmia-related consequences, particularly sudden death. Ventricular tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers for sudden death in highly selected HCM populations.
    Methods: We assessed the profile of ventricular and supraventricular ectopy and bradyarrhythmia on ambulatory 24-h Holter ECG and also related these findings to clinical outcome in 178 HCM patients.
    Results: Of the 178 study patients, 157 (88%) had premature ventricular complexes (PVCs), including 21 (12%) with >/=500 PVCs, 74 (42%) had couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 +/- 763 (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York Heart Association functional classes III and IV) (p = 0.04); SVT occurred more commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5 +/- 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%) including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative and positive predictive values of 95% and 9%, and sensitivity and specificity of 45% and 69%, respectively.
    Conclusions: In this nontertiary-based HCM cohort, ventricular and supraventricular tachyarrhythmias were particularly frequent and demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite such a highly arrhythmogenic substrate, sudden death events proved to be relatively uncommon. Ventricular tachyarrhythmias had a low positive and relatively high negative predictive value for sudden death in this HCM population.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Atrial Premature Complexes/diagnosis ; Atrial Premature Complexes/epidemiology ; Bradycardia/diagnosis ; Bradycardia/epidemiology ; Cardiology Service, Hospital ; Cardiomyopathy, Hypertrophic/diagnosis ; Cardiomyopathy, Hypertrophic/epidemiology ; Child ; Child, Preschool ; Comorbidity ; Death, Sudden, Cardiac/epidemiology ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Hospitals, Community ; Humans ; Male ; Middle Aged ; Minnesota ; Risk Factors ; Survival Analysis ; Tachycardia, Supraventricular/diagnosis ; Tachycardia, Supraventricular/epidemiology ; Tachycardia, Ventricular/diagnosis ; Tachycardia, Ventricular/epidemiology ; Ventricular Premature Complexes/diagnosis ; Ventricular Premature Complexes/epidemiology
    Language English
    Publishing date 2005-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2004.11.043
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  9. Article: Cardiac Magnetic Resonance Imaging for the Assessment of Myocardial Angiogenesis.

    Wilke, Norbert M. / Zenovich, Andrey G. / Jerosch-Herold, Michael / Henry, Timothy D.

    Current interventional cardiology reports

    2001  Volume 3, Issue 3, Page(s) 205–212

    Abstract: Research in biology and applications of growth factors in coronary artery disease (CAD) has progressed considerably over recent years. Vascular endothelial growth factor and fibroblast growth factor-2 have been more successful in animal models of ... ...

    Abstract Research in biology and applications of growth factors in coronary artery disease (CAD) has progressed considerably over recent years. Vascular endothelial growth factor and fibroblast growth factor-2 have been more successful in animal models of myocardial ischemia and Phase I studies than in placebo-controlled trials. However, cardiac magnetic resonance (CMR), with its higher sensitivity and specificity indices for identification of CAD, has not been extensively used in trials of angiogenic therapies. Data in animals and in patients suggest that CMR can reliably identify collateral vessels. Therefore, we hypothesize that CMR may depict collateralization induced by angiogenic therapy better than currently used nuclear perfusion imaging modalities. Versatility of the assessment of myocardial function and perfusion in one imaging session, combined with the noninvasive nature of the test, may considerably lower the cost of clinical trials. Use of CMR-derived surrogate end points may provide better risk stratification and assessment of efficacy in patients receiving growth factor therapy.
    Language English
    Publishing date 2001-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2057364-9
    ISSN 1523-3839
    ISSN 1523-3839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Acute and reversible cardiomyopathy provoked by stress in women from the United States.

    Sharkey, Scott W / Lesser, John R / Zenovich, Andrey G / Maron, Martin S / Lindberg, Jana / Longe, Terrence F / Maron, Barry J

    Circulation

    2005  Volume 111, Issue 4, Page(s) 472–479

    Abstract: Background: A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan.: Methods and results: Over a 32-month ... ...

    Abstract Background: A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan.
    Methods and results: Over a 32-month period, 22 consecutive patients with this novel cardiomyopathy were prospectively identified within a community-based practice in the Minneapolis-St. Paul, Minn, area. All patients were women aged 32 to 89 years old (mean 65+/-13 years); 21 (96%) were > or =50 years of age. The syndrome is characterized by (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing by angiography; (3) systolic dysfunction (ejection fraction 29+/-9%), with abnormal wall motion of the mid and distal LV, ie, "apical ballooning"; and (4) profound psychological stress (eg, death of relatives, domestic abuse, arguments, catastrophic medical diagnoses, devastating financial or gambling losses) immediately preceding and triggering the cardiac events. A significant proportion of patients (37%) had hemodynamic compromise and required vasopressor agents and intra-aortic balloon counterpulsation. Each patient survived with normalized ejection fraction (63+/-6%; P<0.001) and rapid restoration to previous functional cardiovascular status within 6+/-3 days. In 95%, MRI identified diffusely distributed segmental wall-motion abnormalities that encompassed LV myocardium in multiple coronary arterial vascular territories.
    Conclusions: A reversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome. This condition is characterized by a distinctive form of systolic dysfunction that predominantly affects the distal LV chamber and a favorable outcome with appropriate medical therapy.
    MeSH term(s) Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathy, Dilated/diagnosis ; Cardiomyopathy, Dilated/epidemiology ; Cardiomyopathy, Dilated/etiology ; Chest Pain/etiology ; Cohort Studies ; Coronary Angiography ; Diagnosis, Differential ; Electrocardiography ; Female ; Heart Ventricles/pathology ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Minnesota/epidemiology ; Myocardial Infarction/diagnosis ; Prognosis ; Prospective Studies ; Stress, Psychological/complications ; Stress, Psychological/physiopathology ; Stroke Volume ; Syndrome ; Troponin I/blood ; Troponin T/blood ; Ventricular Dysfunction, Left/diagnosis ; Ventricular Dysfunction, Left/epidemiology ; Ventricular Dysfunction, Left/etiology
    Chemical Substances Troponin I ; Troponin T
    Language English
    Publishing date 2005-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/01.CIR.0000153801.51470.EB
    Database MEDical Literature Analysis and Retrieval System OnLINE

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