Jacek Lelakowski

Publication Details
Article Title: [Cardiac arrhythmias and their non-pharmacological treatment in the valvular heart diseases].

First Author: Jacek Lelakowski

All Authors: Lelakowski J

Journal Title: Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego

Abstract: Cardiac arrhythmias most often arise in the mechanism of disorders of impulse formation (automaticity, triggered activity), disorders of impulse conduction (reentry, block) or a combination of both. Atrial fibrillation (AF) most often occurs in the course of mitral stenosis and/or mitral regurgitation, rarely in the defects of the aortic valve. Ventricular arrhythmias may be associated with the most valvular heart diseases. Among the disturbances of automatism and conduction in valvular heart diseases, the most common are atrioventricular blocks (AV blocks) and intraventricular blocks. In addition to defect correction and pharmacological treatment, non-pharmacological treatment of cardiac arrhythmias (transcatheter ablative techniques, permanent pacemakers, implantable cardioverter-defibrillators, implantable cardiac resynchronization devices) plays a significant role in the treatment. It is important for the practitioner to understand about the mechanisms of arrhythmia and nonpharmacological treatment in patients with acquired valvular heart diseases.

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Developmental biology
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Authors: Ballard VL, Mikawa T

Abstract: Cardiac neural crest cells are essential for normal development of the great vessels and the heart, giving rise to a range of cell types, including both neuronal and non-neuronal adventitial cells and smooth muscle. Endothelin (ET) signaling plays an important role in the development of cardiac neural crest cell lineages, yet the underlying mechanisms that act to control their migration, differentiation, and proliferation remain largely unclear. We examined the expression patterns of the receptor, ET(A), and the ET-specific converting enzyme, ECE-1, in the pharyngeal arches and great vessels of the developing chick embryo. In situ hybridization analysis revealed that, while ET(A) is expressed in the pharyngeal arch mesenchyme, populated by cardiac neural crest cells, ECE-1 expression is localized to the outermost ectodermal cells of the arches and then to the innermost endothelial cells of the great vessels. This dynamic pattern of expression suggests that only a subpopulation of neural crest cells in these regions is responsive to ET signaling at particular developmental time points. To test this, retroviral gene delivery was used to constitutively express preproET-1, a precursor of mature ET-1 ligand, in the cardiac neural crest. This resulted in a selective expansion of the outermost, adventitial cell population in the great vessels. In contrast, neither differentiation nor proliferation of neural crest-derived smooth muscle cells was significantly affected. These results suggest that constitutive expression of exogenous preproET-1 in the cardiac neural crest results in expansion restricted to an adventitial cell population of the developing great vessels.

The Annals of thoracic surgery
Vascular growth factors and angiogenesis in cardiac surgery.

Authors: Sellke FW, Ruel M

Abstract: Therapeutic angiogenesis, in the form of growth factor protein administration or gene therapy, has emerged as a new method of treatment for patients with severe, inoperable coronary artery disease. Improved myocardial perfusion and function after administration of angiogenic growth factors has been demonstrated in animal models of chronic myocardial ischemia. Recently, preliminary clinical trials using growth factor proteins or genes encoding these angiogenic factors have demonstrated clinical and other objective evidence of relevant angiogenesis. A recent study reported beneficial long-term effects of therapeutic angiogenesis using fibroblast growth factor (FGF)-2 protein in terms of freedom from angina and perfusion on single-photon emission computed tomographic imaging. Thus, therapeutic angiogenesis has the potential to extend treatment options to patients who are not optimal candidates for conventional methods of myocardial revascularization. However, endogenous antiangiogenic influences, intrinsic lack of response of patients with severe endothelial dysfunction, and other limitations will need to be overcome before angiogenesis becomes a standard therapy for the treatment of patients with severe coronary disease.

Advances in medical sciences
Low-dose dobutamine stress echo for reverse remodeling prediction after cardiac resynchronization.

Authors: Wita K, Mizia-Stec K, P?o?ska-Go?ciniak E, Wróbel W, Gackowski A, G?sior Z, Kasprzak J, Kukulski T, Sinkiewicz W, Wojciechowska C

Abstract: Cardiac resynchronization therapy (CRT) is a valuable option for patients with heart failure and wide QRS to reduce electromechanical dyssynchrony (DYS). High non-responders rate (30%) urges the need to improve selection of candidates for CRT. We hypothesized that low-dose dobutamine stress echocardiography (DSE) can help unmask dyssynchronous motion. The aim of this study is comparison between dyssynchrony index at rest and during low-dose dobutamine stress to predict left ventricular reverse remodeling after CRT.Prospectively, 57 consecutive patients (37 male) aged 61.8±9 who qualified for CRT according to current guidelines were enrolled. Two dimensional echocardiography and tissue Doppler imaging (TDI) were performed before and 6 month after CRT to assess reverse remodeling (rLV). Additionally DSE was performed before CRT. DYS was assessed at rest (DYSr) and peak DSE (DYSd) separately, as a difference between time to peak systolic velocity (Ts) of septum and lateral wall. Ts was corrected for heart rate.rLV defined as decrease ?15% of LVESV at follow-up was found in 38 (67%) patients. DYSr and DYSd were independent predictors of rLV (OR=1.04, Cl ±1.02-1.06, p<0.02 and OR=1.05, Cl±1.03-1.08, p<0.0002 respectively). ROC analysis found that DYSr>42ms and DYSd>59ms had sensitivity of 70% and 87%, specificity of 61% and 78%, and accuracy of 70% and 84% respectively for prediction of reverse remodeling LV. Area under Receiver Operating Characteristic Curve for DYSd was higher than for DYSr (0.89 vs 0.71, p<0.007).Exercise intraventricular dyssynchrony assessed by dobutamine stress echo is a strong independent predictor of cardiac resynchronization therapy response.

Clinical biochemistry
B-type natriuretic peptide secretion without change in intra-cardiac pressure.

Authors: Puelacher C, Rudez J, Twerenbold R, Moreno Weidmann Z, Osswald S, Eckstein F, Lurati-Buse G, Pargger H, Mueller C

Abstract: In clinical cardiology, B-type natriuretic peptide (BNP) is used as a non-invasive surrogate marker for intra-cardiac filling pressures, particularly in patients with heart failure. It is unknown whether and to what extent increase in intravascular volume and/or sympathetic tone while maintaining constant intra-cardiac pressures leads to an increase in levels of BNP in vivo.We aimed to test this hypothesis in an experimental in vivo model of patients directly after off-pump coronary artery bypass grafting admitted to the intensive care unit. These patients require high volumes of intravenous fluids titrated to keep intra-cardiac filling pressures and arterial blood pressure in the normal range while awakening from deep general anesthesia. In 27 consecutive patients, intra-cardiac filling pressures (using a pulmonary artery catheter) and levels of BNP were measured simultaneously every 6h.At 0, 6, 12, and 18h, the pulmonary capillary wedge pressure remained constant (12±4, 13±3, 12±3, and 13±3mmHg, respectively; p=0.351). Similarly, right heart filling pressures did not change during the study period. In contrast, BNP levels increased significantly during the study period: Median levels were 82 [IQR 37-162] pg/ml at 0h, 153 [92-246] pg/ml at 6h, 274 [156-392] pg/ml at 12h, and 320 [200-528] pg/ml at 18h (p<0.001). No significant correlation between BNP levels and pulmonary capillary wedge pressures was found (r=0.052; p=0.604).After cardiac surgery, BNP cannot be considered a reliable non-invasive surrogate for PCWP. In vivo, substantial BNP secretion occurs independently of PCWP in a setting of increasing intravascular volume and consciousness/sympathetic tone.

Circulation research
Bone morphogenetic protein signaling modulates myocardin transactivation of cardiac genes.

Authors: Callis TE, Cao D, Wang DZ

Abstract: Bone morphogenetic proteins (BMPs) play important roles in cardiovascular development. However, how BMP-signaling pathways regulate cardiac gene expression is less clear. We have previously identified myocardin as a cardiac and smooth muscle-specific transcriptional cofactor for serum response factor (SRF). Myocardin potently activates target gene expression by tethering with SRF bound to SRF-responsive elements, the CArG box. Here, we show that Smad1, an effector of the BMP-signaling pathway, synergistically activates myocardin-dependent cardiac gene expression. Interestingly, the CArG box is necessary and sufficient to mediate such synergy, whereas no obvious Smad-binding element appears to be involved. Consistent with their functional interaction, we find that myocardin and Smad1 proteins interact directly. Furthermore, myocardin protein levels were dramatically increased by BMP-2 treatment in cardiomyocytes. These findings suggest myocardin participates in a BMP signaling-dependent cardiac gene transcriptional program.

Clinical laboratory
Performance Evaluation of the FREND Cardiac Triple Cartridge on the FREND System.

Authors: Lee K, Han M, Song SH, Park KU, Song WH, Song J

Abstract: We evaluated the performance of the FREND Cardiac Triple cartridge on the FREND system in the detection of cardiac markers-myoglobin, cardiac troponin I (cTnI), and creatine kinase-MB (CK-MB).Quantitative immunoassays were performed using the FREND system (NanoEnTek, Seoul, Korea) and its cartridge. The precision, detection limits, linearity, and correlation with the Siemens Dimension Vista 500 (Siemens Healthcare Diagnostics, Deerfield, IL, USA) were evaluated. The cutoff value for each marker was calculated in healthy individuals (men and women, n = 138 each).The coefficients of variation for imprecision were less than 19.0% at low and high serum concentrations. The lower limits of quantification for myoglobin, cTnI, and CK-MB were 3.11, 0.073, and 0.70 ng/mL, respectively. Acceptable linearity was achieved for each marker (R2 < 0.99). The results from the FREND system were in good agreement with those from the Siemens Dimension Vista (correlation coefficients > 0.9). The cutoff values in male and female individuals (n = 138 each) were 104.3 and 98.9 ng/mL, respectively, for myoglobin, and 4.35 and 5.37 ng/mL, respectively, for CK-MB. The cutoff value for cTnI was 0.073 ng/mL.The FREND Cardiac Triple cartridge exhibited good precision, clinically acceptable linearity, and reliable correlation with the Dimension Vista.

Journal of cardiac failure
A multicenter study of noninvasive cardiac output by bioreactance during symptom-limited exercise.

Authors: Maurer MM, Burkhoff D, Maybaum S, Franco V, Vittorio TJ, Williams P, White L, Kamalakkannan G, Myers J, Mancini DM

Abstract: Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF.A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO(2), cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO(2) (pVO(2)) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min)=19.6+4.M -2.1.NYHA+1.9.G -0.09.Age, where M=1 for treadmill and 0 for bicycle and G=1 for males and 0 for females. Similarly, pVO(2) (mL/kg/min)=24+2.1.M -2.9.NYHA+1.26.G -0.08.Age. VO(2) and CO were also highly correlated to each other: pCO (mL/kg/min)=0.059+0.007.pVO(2)+0.036.M -0.025.G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO(2) (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance.Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO(2) and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.

Journal of hypertension
Cardiac mast cells in the transition to heart failure: innocent bystanders or key actors?

Authors: Palladini G, Tozzi R, Perlini S


Pediatric cardiology
Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with congenital factor XI deficiency.

Authors: Avci Z, Malbora B, Gokdemir M, Ozkan S, Ozbek N

Abstract: We report our experience with the use of recombinant activated factor VII (rFVIIa) during cardiac surgery in a 4.5-year-old boy with severe congenital FXI deficiency and a congenital heart disease. After weaning the patient from cardiopulmonary bypass, the first intravenous dose of rFVIIa (90 microg/kg) was administered. This same dosage was repeated eight more times, at 2- to 4-hour intervals postoperatively. There was no bleeding during and after surgery. rFVIIa treatment may be used successfully in children with severe FXI deficiency in major operations such as open heart surgery.

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
Evaluation of transpulmonary thermodilution as a method to measure cardiac output in anesthetized cats.

Authors: Beaulieu KE, Kerr CL, McDonell WN

Abstract: The objectives of this study were to evaluate the use of a transpulmonary thermodilution (Trans) technique for the measurement of cardiac output, and to determine the agreement between Trans and conventional thermodilution (TD) in anesthetized cats. Using each technique, cardiac output was measured in 5 mature cats (weights 2.4 to 5.6 kg) anesthetized with isoflurane. To induce different levels of cardiac output in each cat, anesthesia was maintained at > 1.5x end-tidal minimum alveolar concentration (MAC) of isoflurane, and at 1.3x end-tidal isoflurane MAC with and without administration of dobutamine. At least 2 comparisons between TD and Trans values were made at each cardiac output rate. Thirty-two of the 42 recorded comparisons were analyzed. Linear regression analysis (TD vs Trans) yielded an r(2) value of 0.83. The mean bias (TD-Trans) was -3.7 mL/kg/min with limits of agreement of -35.9 to 28.5 mL/kg/min. The concordance coefficient was 0.91. The Trans method showed good relationship and good agreement with TD in anesthetized cats. The Trans method is a relatively noninvasive, practical, and safe method to measure cardiac output in anesthetized cats.

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