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  • Ovid Technologies (Wolters Kluwer Health)  (35)
  • 1
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    Utility of Doppler Echocardiography and Tissue Doppler Imaging in the Estimation of Diastolic Function in Heart Failure With Normal Ejection Fraction : A Comparative Doppler-Conductance Catheterization Study
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. 6 ( 2007-08-07), p. 637-647
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. 6 ( 2007-08-07), p. 637-647
    Abstract: Background— Various conventional and tissue Doppler echocardiographic indexes were compared with pressure–volume loop analysis to assess their accuracy in detecting left ventricular (LV) diastolic dysfunction in patients with heart failure with normal ejection fraction (HFNEF). Methods and Results— Diastolic dysfunction was confirmed by pressure–volume loop analysis obtained by conductance catheter in 43 patients (19 men) with HFNEF. Their Doppler indexes were compared with those of 12 control patients without heart failure symptoms and with normal ejection fraction. Invasively measured indexes for diastolic relaxation (τ, dP/dt min ), LV end-diastolic pressure, and LV end-diastolic pressure–volume relationship (stiffness, b [dP/dV], and stiffness constant, β) were correlated with several conventional mitral flow and tissue Doppler imaging indexes. Conventional Doppler indexes correlated moderately with the degree of LV relaxation index, τ (E/A: r =−0.36, P =0.013; isovolumic relaxation time: r =0.31, P =0.040) and b (deceleration time: r =0.39, P =0.012) but not with β, in contrast to the tissue Doppler imaging indexes E’/A’ lateral ( r =−0.37, P =0.008) and E/E’ lateral ( r =0.53, P 〈 0.001). Diastolic dysfunction was detected in 70% of the HFNEF patients by mitral flow Doppler but in 81% and 86% by E’/A’ lateral , and E/E’ lateral , respectively. Conclusions— Of all echocardiographic parameters investigated, the LV filling index E/E’ lateral was identified as the best index to detect diastolic dysfunction in HFNEF in which the diagnosis of diastolic dysfunction was confirmed by conductance catheter analysis. We recommend its use as an essential tool for noninvasive diagnostics of diastolic function in patients with HFNEF.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.106.661983
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
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  • 2
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    Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 117, No. 16 ( 2008-04-22), p. 2051-2060
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 16 ( 2008-04-22), p. 2051-2060
    Abstract: Background— Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and during atrial pacing and handgrip exercise. Methods and Results— Patients with HFNEF (n=70) and patients without heart failure symptoms (n=20) were enrolled. Pressure-volume loops were measured with a conductance catheter during basal conditions, handgrip exercise, and atrial pacing with 120 bpm to analyze diastolic and systolic left ventricular function. During transient preload reduction, the diastolic stiffness constant was measured directly. Diastolic function with increased stiffness was significantly impaired in patients with HFNEF during basal conditions. This was associated with increased end-diastolic pressures during handgrip exercise and with decreased stroke volume and a leftward shift of pressure-volume loops during atrial pacing. Conclusions— Increased left ventricular stiffness contributed to increased end-diastolic pressure during handgrip exercise and decreased stroke volume during atrial pacing in patients with HFNEF. These data suggest that left ventricular stiffness modulates cardiac function in HFNEF patients and suggests that diastolic dysfunction with increased stiffness is a target for treating HFNEF.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.716886
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
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  • 3
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    Prevention of Cardiac Dysfunction in Acute Coxsackievirus B3 Cardiomyopathy by Inducible Expression of a Soluble Coxsackievirus-Adenovirus Receptor
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation Vol. 120, No. 23 ( 2009-12-08), p. 2358-2366
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 120, No. 23 ( 2009-12-08), p. 2358-2366
    Abstract: Background— Group B coxsackieviruses (CVBs) are the prototypical agents of acute myocarditis and chronic dilated cardiomyopathy, but an effective targeted therapy is still not available. Here, we analyze the therapeutic potential of a soluble (s) virus receptor molecule against CVB3 myocarditis using a gene therapy approach. Methods and Results— We generated an inducible adenoviral vector (AdG12) for strict drug-dependent delivery of sCAR-Fc, a fusion protein composed of the coxsackievirus-adenovirus receptor (CAR) extracellular domains and the carboxyl terminus of human IgG1-Fc. Decoy receptor expression was strictly doxycycline dependent, with no expression in the absence of an inducer. CVB3 infection of HeLa cells was efficiently blocked by supernatant from AdG12-transduced cells, but only in the presence of doxycycline. After liver-specific transfer, AdG12 (plus doxycycline) significantly improved cardiac contractility and diastolic relaxation compared with a control vector in CVB3-infected mice if sCAR-Fc was induced before infection (left ventricular pressure 59±3.8 versus 45.4±2.7 mm Hg, median 59 versus 45.8 mm Hg, P 〈 0.01; dP/dt max 3645.1±443.6 versus 2057.9±490.2 mm Hg/s, median 3526.6 versus 2072 mm Hg/s, P 〈 0.01; and dP/dt min −2125.5±330.5 versus −1310.2±330.3 mm Hg/s, median −2083.7 versus −1295.9 mm Hg/s, P 〈 0.01) and improved contractility if induced concomitantly with infection (left ventricular pressure 76.4±19.2 versus 56.8±10.3 mm Hg, median 74.8 versus 54.4 mm Hg, P 〈 0.05; dP/dt max 5214.2±1786.2 versus 3011.6±918.3 mm Hg/s, median 5182.1 versus 3106.6 mm Hg/s, P 〈 0.05), respectively. Importantly, hemodynamics of animals treated with AdG12 (plus doxycycline) were similar to uninfected controls. Preinfection induction of sCAR-Fc completely blocked and concomitant induction strongly reduced cardiac CVB3 infection, myocardial injury, and inflammation. Conclusion— AdG12-mediated sCAR-Fc delivery prevents cardiac dysfunction in CVB3 myocarditis under prophylactic and therapeutic conditions.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.108.845339
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 4
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    Complication Rate of Right Ventricular Endomyocardial Biopsy via the Femoral Approach : A Retrospective and Prospective Study Analyzing 3048 Diagnostic Procedures Over an 11-Year Period
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. 17 ( 2008-10-21), p. 1722-1728
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. 17 ( 2008-10-21), p. 1722-1728
    Abstract: Background— An unequivocal diagnosis of myocarditis and cardiac virus persistence is based on histological, immunohistological, and molecular biological analyses of endomyocardial biopsies (EMBs). Biopsy-based diagnosis of myocarditis has become increasingly important because recent studies have demonstrated the beneficial effects of biopsy-based causal treatment strategies (immunosuppressive or antiviral). Because the risks of major complications caused by EMB procedures have not yet been well defined, we evaluated the incidence of major and minor complications of right ventricular EMB procedures in this retrospective and prospective single-center study. Methods and Results— With the use of a modified Cordis bioptome, 1919 patients underwent 2505 EMB procedures retrospectively over a 9-year period (January 1995 to December 2003), and 496 patients underwent 543 EMB procedures prospectively between January 2004 and December 2005. A total of 2415 patients had 3048 EMB procedures via the right femoral vein approach under biplane fluoroscopic control to evaluate unexplained left ventricular dysfunction (retrospective left ventricular ejection fraction, 49.8±18.8%; prospective, 48.8±19.7%) after exclusion of secondary causes. During each EMB procedure, an average of 8.2±0.8 EMBs were obtained retrospectively and 10.1±0.6 specimens prospectively for a total of 26 025 specimens. No patient died or required emergency cardiac surgery. Other major complications like cardiac tamponade requiring pericardiocentesis or complete atrioventricular block requiring permanent pacing were very rare: 0.12% in the retrospective study and 0% in the prospective study. Minor complications such as pericardial effusion, conduction abnormalities, or arrhythmias occurred in 0.20% of the EMB procedures in the retrospective study and 5.5% in the prospective study. Conclusions— The EMB procedure via the femoral vein approach under fluoroscopic guidance has a very low complication rate when performed by experienced operators.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.743427
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
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  • 5
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    Response to Letter Regarding Article, “Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction”
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation Vol. 119, No. 1 ( 2009-01-06)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 1 ( 2009-01-06)
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.108.803429
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 6
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    Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation: Heart Failure Vol. 8, No. 3 ( 2015-05), p. 605-618
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 3 ( 2015-05), p. 605-618
    Abstract: Investigation of disease pathogenesis confined to protein-coding regions of the genome may be incomplete because many noncoding variants are associated with disease. We aimed to identify novel predictive markers for the course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements influencing the grossly different antiviral capacity of individual patients. Methods and Results— Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared with those with virus persistence on follow-up. miR profiling revealed highly significant differences in cardiac levels of 16 miRs, but not of protein-coding genes. Evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate receiver operating characteristic curve analysis, confirmed this pattern as highly predictive for disease course (area under the curve, 0.897±0.071; 95% confidence interval, 0.758–1.000). Eight miRs were strongly induced in CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. They are predicted to target multiple immune response genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b, 190, and 422a in the monocytic THP-1 cell line. Conclusions— An immediate clinical application of the data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.114.001475
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2428100-1
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  • 7
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    Induction of Coxsackievirus-Adenovirus–Receptor Expression During Myocardial Tissue Formation and Remodeling : Identification of a Cell-to-Cell Contact–Dependent Regulatory Mechanism
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Circulation Vol. 107, No. 6 ( 2003-02-18), p. 876-882
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 107, No. 6 ( 2003-02-18), p. 876-882
    Abstract: Background— The coxsackievirus-adenovirus receptor (CAR) was cloned as a receptor for both viruses, but its primary biological functions and regulatory mechanisms are unknown. CAR was low in healthy adult myocardium, whereas strong CAR reexpression was observed in human dilated cardiomyopathy. The molecular mechanisms of CAR induction in cardiomyocytes are unknown. Methods and Results— We report on CAR regulation during development, CAR induction after myocardial infarction, and cell-to-cell contact–dependent CAR regulation in the rat. The high CAR expression during development in various organs decreased up to 190-fold after birth. After infarction resulting in severe cardiac dysfunction (dP/dt max , −53%; dP/dt min , −58%; left ventricular pressure, −45%), CAR was induced locally in cardiomyocytes of the infarct zone, where it was also expressed by capillary-like CD31 + structures and CD18 + interstitial cells, whereas it remained confined to subendothelial layers of arterioles and venules. In cultured cardiomyocytes, endothelin-1, cardiotrophin-1, leukemia-inhibiting factor, and cyclic stretch had no effect on CAR, whereas at high versus low cell density, CAR was suppressed up to 10-fold ( P =0.006). Conditioned media from low- or high-density cardiomyocytes or cardiofibroblasts had no effect. Conclusions— The locally confined CAR upregulation after infarction makes induction by various humoral factors unlikely, because cardiac dysfunction results in high activities of sympathetic and renin-angiotensin systems and cytokines. The cell culture experiments identify a cell-to-cell contact–dependent mechanism of CAR regulation. Further characterization of the signals linking cell-to-cell interactions to CAR gene expression may provide insight into mechanisms and functional consequences of the generalized CAR induction in dilated cardiomyopathy, and of its local induction after myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000050150.27478.C5
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
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  • 8
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    Cardiac Inflammation Contributes to Changes in the Extracellular Matrix in Patients With Heart Failure and Normal Ejection Fraction
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Circulation: Heart Failure Vol. 4, No. 1 ( 2011-01), p. 44-52
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 4, No. 1 ( 2011-01), p. 44-52
    Abstract: The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF. Methods and Results— We investigated left ventricular systolic and diastolic function in 20 patients with HFNEF and 8 control patients by conductance catheter methods and echocardiography. Endomyocardial biopsy samples were also obtained, and ECM proteins as well as cardiac inflammatory cells were investigated. Primary human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to investigate the gene expression of ECM proteins after stimulation with transforming growth factor-β. Diastolic dysfunction was present in the HFNEF patients compared with the control patients. In endomyocardial biopsy samples from HFNEF patients, we found an accumulation of cardiac collagen, which was accompanied by a decrease in the major collagenase system (matrix metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells, which expressed the profibrotic growth factor transforming growth factor-β, could be documented in the HFNEF patients. Stimulation of primary human cardiac fibroblasts from HFNEF patients with transforming growth factor-β resulted in transdifferentiation of fibroblasts to myofibroblasts, which produced more collagen and decreased the amount of matrix metalloproteinase-1, the major collagenase in the human heart. A positive correlation between cardiac collagen, as well as the amount of inflammatory cells, and diastolic dysfunction was evident and suggests a direct influence of inflammation on fibrosis triggering diastolic dysfunction. Conclusions— Cardiac inflammation contributes to diastolic dysfunction in HFNEF by triggering the accumulation of ECM.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.109.931451
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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  • 9
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    Application of Magnetocardiography to Screen for Inflammatory Cardiomyopathy and Monitor Treatment Response
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American Heart Association Vol. 12, No. 4 ( 2023-02-21)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 4 ( 2023-02-21)
    Abstract: Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine‐related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine‐related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days ( P =0.010) and to 0.03 within 30 days ( P 〈 0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% ( P 〈 0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.122.027619
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2653953-6
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  • 10
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    Cardiovascular RNA Interference Therapy : The Broadening Tool and Target Spectrum
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation Research Vol. 113, No. 5 ( 2013-08-16), p. 588-602
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 113, No. 5 ( 2013-08-16), p. 588-602
    Abstract: Understanding of the roles of noncoding RNAs (ncRNAs) within complex organisms has fundamentally changed. It is increasingly possible to use ncRNAs as diagnostic and therapeutic tools in medicine. Regarding disease pathogenesis, it has become evident that confinement to the analysis of protein-coding regions of the human genome is insufficient because ncRNA variants have been associated with important human diseases. Thus, inclusion of noncoding genomic elements in pathogenetic studies and their consideration as therapeutic targets is warranted. We consider aspects of the evolutionary and discovery history of ncRNAs, as far as they are relevant for the identification and selection of ncRNAs with likely therapeutic potential. Novel therapeutic strategies are based on ncRNAs, and we discuss here RNA interference as a highly versatile tool for gene silencing. RNA interference-mediating RNAs are small, but only parts of a far larger spectrum encompassing ncRNAs up to many kilobasepairs in size. We discuss therapeutic options in cardiovascular medicine offered by ncRNAs and key issues to be solved before clinical translation. Convergence of multiple technical advances is highlighted as a prerequisite for the translational progress achieved in recent years. Regarding safety, we review properties of RNA therapeutics, which may immunologically distinguish them from their endogenous counterparts, all of which underwent sophisticated evolutionary adaptation to specific biological contexts. Although our understanding of the noncoding human genome is only fragmentary to date, it is already feasible to develop RNA interference against a rapidly broadening spectrum of therapeutic targets and to translate this to the clinical setting under certain restrictions.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.113.301056
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467838-X
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