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  1. Article ; Online: Association Between Family History and Early-Onset Atrial Flutter Across Racial and Ethnic Groups.

    Shah, Anish S / Ongtengco, Ana / Qiao, Victor / Chen, Yining / Diaz, Annette / Hill, Michael / Bhan, Adarsh / Tofovic, David S / Darbar, Dawood

    Journal of the American Heart Association

    2024  , Page(s) e032320

    Abstract: Background: Genetic and familial contributions to early-onset atrial fibrillation are described primarily in individuals of European ancestry. However, the role of racial and familial contributions in the pathogenesis of early-onset atrial flutter ( ... ...

    Abstract Background: Genetic and familial contributions to early-onset atrial fibrillation are described primarily in individuals of European ancestry. However, the role of racial and familial contributions in the pathogenesis of early-onset atrial flutter (EOAFL) is unclear.
    Methods and results: In this cross-sectional study, participants were enrolled prospectively from 2015 to 2021 in multiple academic centers with a diagnosis of atrial flutter (AFL) confirmed by ECG. EOAFL was defined as a diagnosis of AFL before age 66 years with no concomitant or previous diagnosis of atrial tachyarrhythmias. Family history was adjudicated through baseline questionnaires and direct family interviews about the diagnosis of atrial tachyarrhythmias, stroke, and cardiomyopathy. The primary exposure was a positive family history in first-degree relatives, and the primary outcome was the odds of EOAFL versus late-onset AFL. A total of 909 patients were enrolled. Participants with a positive family history of atrial tachyarrhythmias were younger, less likely to be of Black race, and more likely to have EOAFL. The adjusted odds ratio (OR) for EOAFL in those with a positive family history was 1.8 (95% CI, 1.1-3.0). There was an increased odds of EOAFL in those of Black race (OR, 2.1 [95% CI, 1.4-3.2]), alcohol use (OR, 1.6 [95% CI, 1.0-2.6]), and obstructive sleep apnea (OR, 1.9 [95% CI, 1.0-3.4]). Use of cardioselective β blockers or calcium channel blockers before the diagnosis of AFL were associated with a lower odds of EOAFL (OR, 0.5 [95% CI, 0.2-0.9]).
    Conclusions: These findings suggest a potentially hereditary predisposition to EOAFL across race and ethnicity, warranting further study of the genetic contributions to AFL.
    Language English
    Publishing date 2024-05-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.123.032320
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Current Status of Inotropes in Heart Failure.

    Ginwalla, Mahazarin / Tofovic, David S

    Heart failure clinics

    2018  Volume 14, Issue 4, Page(s) 601–616

    Abstract: Inotropes are medications that improve the contractility of the heart and are used in patients with low cardiac output or evidence of end-organ dysfunction. Since their initial discovery, inotropes have held promise in alleviating symptoms and ... ...

    Abstract Inotropes are medications that improve the contractility of the heart and are used in patients with low cardiac output or evidence of end-organ dysfunction. Since their initial discovery, inotropes have held promise in alleviating symptoms and potentially increasing longevity in such patients. Decades of intensive study have further elucidated the benefits and risks of using inotropes. In this article, the authors discuss the history of inotropes, their indications, mechanism of action, and current guidelines pertaining to their use in heart failure. The authors provide insight into their appropriate use and related shortcomings and the practical aspects of inotrope use.
    MeSH term(s) Cardiac Output, Low/drug therapy ; Cardiac Output, Low/etiology ; Cardiac Output, Low/physiopathology ; Cardiotonic Agents/therapeutic use ; Heart Failure/complications ; Heart Failure/drug therapy ; Heart Failure/physiopathology ; Humans ; Treatment Outcome ; Ventricular Function/drug effects ; Ventricular Function/physiology
    Chemical Substances Cardiotonic Agents
    Language English
    Publishing date 2018-08-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2212019-1
    ISSN 1551-7136
    ISSN 1551-7136
    DOI 10.1016/j.hfc.2018.06.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cardiac effects 2 years after successful non-myeloablative human leukocyte antigen-matched related donor hematopoietic cell transplants in sickle cell disease.

    Sachdev, Vandana / Limerick, Emily / Nguyen, My-Le / Li, Wen / Jeffries, Neal / Ramachandra, Shalini / Tofovic, David / Rondelli, Damiano / Al Zahrani, Mohsen / Aljizeeri, Ahmed / Saraf, Santosh / Hsieh, Matthew / Fitzhugh, Courtney D

    American journal of hematology

    2023  Volume 98, Issue 8, Page(s) E219–E221

    MeSH term(s) Humans ; Hematopoietic Stem Cell Transplantation ; Anemia, Sickle Cell/therapy ; HLA Antigens ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease
    Chemical Substances HLA Antigens
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26985
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Waitlist Mortality of Patients With Amyloid Cardiomyopathy who Are Listed for Heart Transplantation and Implications for Organ Allocation.

    Panhwar, Muhammad S / Al-Kindi, Sadeer G / Tofovic, David / Oliveira, Guilherme H / Ginwalla, Mahazarin

    Journal of cardiac failure

    2019  Volume 25, Issue 9, Page(s) 767–771

    Abstract: Background: Outcomes of patients with amyloid cardiomyopathy (ACM) undergoing heart transplantation have been reported, but there are scant data concerning the waitlist mortality (WLM) of these patients.: Aim: The aim of this study was to investigate ...

    Abstract Background: Outcomes of patients with amyloid cardiomyopathy (ACM) undergoing heart transplantation have been reported, but there are scant data concerning the waitlist mortality (WLM) of these patients.
    Aim: The aim of this study was to investigate whether patients with ACM have higher waitlist mortality compared to those with other types of cardiomyopathies.
    Methods: We queried the United Network for Organ Sharing registry for all patients (age ≥ 18 years) listed for heart transplantation between 2008 and 2015. We compared patients with ACM to those with dilated cardiomyopathy (DCM) or idiopathic restrictive cardiomyopathy (RCM) for WLM and waitlist mortality or delisting for deterioration (WLM/D). We identified 306 patients with ACM, 183 with RCM and 8416 with DCM. Patients with ACM were older (ACM 61 vs RCM 49 vs DCM 51 years, P  <  .001), were more likely to be male (82% vs 60% vs 73%, P  <  .001) but less likely to be listed as status 1A (16% vs 18% vs 23%, P< .001). After adjusting for baseline characteristics, ACM was associated with increased risk of mortality and mortality/delisting compared with DCM (HR 2.03 [1.36-3.04], P = .001 for WLM; HR 2.07 [1.55-2.78], P < .001 for WLM/D) but not with other RCMs (HR 1.28 [0.54-3.02], P = .58 for WLM; HR 0.97 [0.56-1.69], P = .91 for WLM/D).
    Results: Patients with ACM are listed with lower acuity and have higher waitlist mortality compared with those with dilated cardiomyopathies. Further studies are needed to identify whether special prioritization should be considered for patients with ACM listed for heart transplantation.
    MeSH term(s) Amyloidosis/complications ; Cardiomyopathies/complications ; Female ; Heart Failure/etiology ; Heart Failure/mortality ; Heart Failure/physiopathology ; Heart Failure/surgery ; Heart Transplantation/methods ; Humans ; Male ; Middle Aged ; Patient Acuity ; Registries/statistics & numerical data ; Risk Factors ; Tissue and Organ Procurement/methods ; United States ; Waiting Lists/mortality
    Language English
    Publishing date 2019-04-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1281194-4
    ISSN 1532-8414 ; 1071-9164
    ISSN (online) 1532-8414
    ISSN 1071-9164
    DOI 10.1016/j.cardfail.2019.04.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Association of Rare Genetic Variants and Early-Onset Atrial Fibrillation in Ethnic Minority Individuals.

    Chalazan, Brandon / Mol, Denise / Darbar, Faisal A / Ornelas-Loredo, Aylin / Al-Azzam, Bahaa / Chen, Yining / Tofovic, David / Sridhar, Arvind / Alzahrani, Zain / Ellinor, Patrick / Darbar, Dawood

    JAMA cardiology

    2021  Volume 6, Issue 7, Page(s) 811–819

    Abstract: Importance: Although rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic ... ...

    Abstract Importance: Although rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity.
    Objectives: To assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations.
    Design, setting, and participants: In this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged ≤66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes. Recruitment took place from July 1, 2015, to June 30, 2019. Data were analyzed from February 1 to February 28, 2020.
    Exposures: Rare and novel variants categorized as pathogenic or likely pathogenic.
    Main outcomes and measures: The prevalence of rare and novel pathogenic variants in African American and Hispanic/Latinx probands with early-onset AF and genotype-phenotype associations.
    Results: Among 227 probands with early-onset AF, mean (SD) age at onset of AF was 51.0 (9.9) years, 132 probands (58.1%) were men, 148 (65.2%) were African American, and 79 (34.8%) were Hispanic/Latinx. A family history of AF was verified in 24 probands with early-onset AF (10.6%). Sequencing 60 candidate genes identified 53 (23 rare and 30 novel) variants with 16 of the 227 (7.0%) probands harboring likely pathogenic (43.8%) or pathogenic (56.2%) variants, with most loss-of-function variants in TTN, the gene encoding the sarcomeric protein titin (46.7%). In 6 families with more than 2 affected members, variants of unknown significance in sodium channel (SCN10A), potassium channel (KCNE5), sarcomeric proteins (MYH6 and TTN), and atrial natriuretic peptide (NPPA) cosegregated with AF.
    Conclusions and relevance: In this study, likely pathogenic and pathogenic variants were identified, with most loss-of-function variants in TTN, that increase susceptibility to early-onset AF in African American and Hispanic/Latinx individuals. These findings provide further understanding toward molecular phenotyping of AF and suggest novel mechanism-based therapeutic approaches for this common arrhythmia in ethnic minority groups.
    MeSH term(s) African Americans/genetics ; African Americans/statistics & numerical data ; Age of Onset ; Atrial Fibrillation/genetics ; Connectin/genetics ; Female ; Genes/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Hispanic or Latino/genetics ; Hispanic or Latino/statistics & numerical data ; Humans ; Loss of Function Mutation/genetics ; Male ; Middle Aged ; Whites/genetics ; Whites/statistics & numerical data
    Chemical Substances Connectin ; TTN protein, human
    Language English
    Publishing date 2021-05-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2380-6591
    ISSN (online) 2380-6591
    DOI 10.1001/jamacardio.2021.0994
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Sitagliptin augments angiotensin II-induced renal vasoconstriction in kidneys from rats with metabolic syndrome.

    Tofovic, David S / Bilan, Victor P / Jackson, Edwin K

    Clinical and experimental pharmacology & physiology

    2010  Volume 37, Issue 7, Page(s) 689–691

    Abstract: 1. Dipeptidyl peptidase (DPP) IV inhibitors enhance renovascular responses to angiotensin (Ang) II in spontaneously hypertensive rats (SHR), but not Wistar-Kyoto rats. Because DPPIV inhibitors are often used in metabolic syndrome, it is important to ... ...

    Abstract 1. Dipeptidyl peptidase (DPP) IV inhibitors enhance renovascular responses to angiotensin (Ang) II in spontaneously hypertensive rats (SHR), but not Wistar-Kyoto rats. Because DPPIV inhibitors are often used in metabolic syndrome, it is important to determine whether DPPIV inhibition in this setting enhances renovascular responses to AngII. 2. Six-week-old Lean-ZSF1 rats (harbouring SHR genes, but without metabolic syndrome; n = 11) and Obese-ZSF1 rats (harbouring SHR genes and expressing metabolic syndrome; n = 10) were provided food and water ad libitum, and metabolic parameters and renovascular responses to AngII were assessed when the animals were 7 and 8 weeks of age, respectively. 3. At 7 weeks of age, compared with Lean-ZSF1, Obese-ZSF1 demonstrated significant (P < 0.05) increases in bodyweight (262 +/- 8 vs 310 +/- 13 g), plasma glucose (112 +/- 4 vs 153 +/- 9 mg/dL), haemoglobin A1c (4.7 +/- 0.1 vs 5.8 +/- 0.4%), urinary glucose excretion (0.021 +/- 0.003 vs 6.70 +/- 1.80 g/kg bodyweight per 24 h) and urinary protein excretion (100 +/- 7 vs 313 +/- 77 mg/kg bodyweight per 24 h). Mean blood pressure was high (133 +/- 7 mmHg) in both strains. 4. At 8 weeks of age, kidneys were isolated and perfused. In Lean-ZSF1 rats, renovascular responses (i.e. changes in perfusion pressure) to physiological levels of AngII (0.1 nmol/L) were 3.4 +/- 1.3 and 18.2 +/- 5.9 mmHg in untreated (n = 5) and 1 micromol/L sitagliptin-treated (n = 6) kidneys, respectively. In Obese-ZSF1 rats, renovascular responses to AngII were 5.5 +/- 1.3 and 17.8 +/- 8.2 mmHg in untreated (n = 4) and sitagliptin-treated (n = 6) kidneys, respectively. Analysis of variance revealed a significant (P = 0.0367) effect of sitagliptin on renovascular responses to AngII that was independent of strain. 5. In conclusion, sitagliptin enhances renovascular responses to AngII in rats harbouring SHR genes and this effect persists in rats with diabetic nephropathy and metabolic syndrome.
    MeSH term(s) Angiotensin II/pharmacology ; Animals ; Blood Glucose/drug effects ; Body Weight/drug effects ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Glycated Hemoglobin A/analysis ; Hypertension/drug therapy ; Hypertension/genetics ; Kidney/blood supply ; Kidney/drug effects ; Male ; Metabolic Syndrome/drug therapy ; Metabolic Syndrome/genetics ; Proteinuria/drug therapy ; Pyrazines/pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Renal Circulation/drug effects ; Sitagliptin Phosphate ; Triazoles/pharmacology ; Vasoconstriction/drug effects ; Vasoconstriction/genetics ; Vasoconstrictor Agents/pharmacology
    Chemical Substances Blood Glucose ; Dipeptidyl-Peptidase IV Inhibitors ; Glycated Hemoglobin A ; Pyrazines ; Triazoles ; Vasoconstrictor Agents ; Angiotensin II (11128-99-7) ; Sitagliptin Phosphate (TS63EW8X6F)
    Language English
    Publishing date 2010-03-30
    Publishing country Australia
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 189277-0
    ISSN 1440-1681 ; 0305-1870 ; 0143-9294
    ISSN (online) 1440-1681
    ISSN 0305-1870 ; 0143-9294
    DOI 10.1111/j.1440-1681.2010.05389.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cardiovascular evaluation and management of iron overload cardiomyopathy in sickle cell disease.

    Ginwalla, Mahazarin / AlMasoud, Abdullah / Tofovic, David / Alin, Tara / Al-Kindi, Sadeer / Oliveira, Guilherme / Rajagopalan, Sanjay / Schilz, Robert / Little, Jane

    American journal of hematology

    2017  Volume 93, Issue 1, Page(s) E7–E9

    MeSH term(s) Anemia, Sickle Cell/complications ; Cardiomyopathies/etiology ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/etiology ; Disease Management ; Humans ; Iron Overload/etiology
    Language English
    Publishing date 2017-10-23
    Publishing country United States
    Document type Letter
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.24924
    Database MEDical Literature Analysis and Retrieval System OnLINE

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