Publications by authors named "Ramon Martos"

18 Publications

  • Page 1 of 1

Practical tips and tricks for assessing prosthetic valves and detecting paravalvular regurgitation using cardiac CT.

J Cardiovasc Comput Tomogr 2014 Jul-Aug;8(4):323-7. Epub 2014 Jul 11.

Cardiac CT/MRI Program, Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland. Electronic address:

Paravalvular leaks are an uncommon but serious complication of prosthetic valves. Transthoracic echocardiography is used in the assessment of prosthetic valves but can be limited by acoustic shadowing from the prosthesis and poor acoustic windowing. Small case series have previously shown cardiac CT to have promising results in detecting paravalvular leaks. We assessed 32 valves in our institution on cardiac CT using echocardiography results as standard and developed methods for improved evaluation of prosthetic valves. These include optimizing prescan drug therapy for heart rate control, optimum window and center adjustments, and carefully selected image planes to best demonstrate the valve ring and valve annulus. Recognition of surgical material is also important to recognize. In this review, we provide a detailed description of these techniques with imaging examples of prosthetic valve evaluation using cardiac CT.
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http://dx.doi.org/10.1016/j.jcct.2014.07.001DOI Listing
May 2015

Successful recanalization of a blind stumpless aorto-ostial left main chronic total occlusion.

Int J Cardiol 2014 Oct 13;176(3):e94-5. Epub 2014 Aug 13.

Department of Cardiology, Hospital Clinico San Carlos, Madrid, Spain.

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http://dx.doi.org/10.1016/j.ijcard.2014.07.295DOI Listing
October 2014

Treating Refractory Hypertension: Renal Denervation With High-Resolution 3D-Angiography.

Res Cardiovasc Med 2013 May 20;2(2):106-8. Epub 2013 May 20.

Department of Cardiology and Interventional Cardiology, Torrejon University Hospital, Madrid, Spain.

A 53-year-old male was referred to our Department for refractory primary hypertension. Despite high doses of 6 anti-hypertensive drugs, ambulatory monitoring of blood pressure (BP) revealed a mean BP of 160/90 mmHg. Under local anaesthesia, renal denervation with radiofrequency was performed supported by high-resolution 3D angiography, which helped confirm the position of the applications in a spiroid fashion.
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http://dx.doi.org/10.5812/cardiovascmed.9700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253761PMC
May 2013

Increase in J-CTO lesion complexity score explains the disparity between recanalisation success and evolution of chronic total occlusion strategies: insights from a single-centre 10-year experience.

Heart 2013 Apr 2;99(7):474-9. Epub 2013 Feb 2.

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK.

Objective: To investigate whether treatment of lesions of greater complexity is now undertaken and to assess the rates of procedural success per class of lesion complexity.

Design: Observational study.

Setting: Despite impressive progress in treatment strategies and equipment, the success rate of percutaneous coronary intervention for chronic total occlusion (CTO) has remained relatively stable.

Participants: 483 patients consecutively treated with CTO from 2003 to 2012.

Main Outcome Measures: The Multicenter CTO Registry of Japan (J-CTO) score was used to classify lesion complexity. The study population was subdivided into an early (period 1, n=288) and a late (period 2, n=195) period according to the routine implementation of novel techniques and advanced equipment.

Results: Period 2 was marked by more 'difficult' and 'very difficult' lesions (J-CTO grades 2 and 3) being attempted, with procedural success increasing from 68.4% to 88.1% (p<0.001) and from 42.0% to 78.9% (p<0.001), respectively. 'Easy' and 'intermediate' lesions (J-CTO grades 0 and 1) were less common, but with similarly high success rates (89.1% vs 96.6% (p=0.45) for easy, and 86.3% vs 86.1% (p=0.99) for intermediate). Period 2 was characterised by a trend for more successful procedures overall (by 6.1%, p=0.09). Procedural complications were similarly low in both periods. J-CTO score and technical era were identified as independent correlates of success in the total population by logistic regression analysis.

Conclusions: Advanced CTO techniques and equipment have resulted in an increase in the successful treatment of highly complex lesions. Total success rate did not substantially improve, as it was counterbalanced by the increased rate at which complex lesions were attempted.
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http://dx.doi.org/10.1136/heartjnl-2012-303205DOI Listing
April 2013

Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

PLoS One 2012 12;7(11):e49259. Epub 2012 Nov 12.

Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin, Ireland.

In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049259PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495762PMC
May 2013

Thrombosed prosthetic valve in Ebstein's anomaly: Evaluation with echocardiography and 64-slice cardiac computed tomography.

World J Cardiol 2012 Jul;4(7):240-1

Ailbhe C O'Neill, Colin J McCarthy, Jonathan D Dodd, Departments of Radiology, St. Vincent's University Hospital, Dublin 4, Ireland.

Ebstein's anomaly (EA) is a rare cardiac congenital malformation with displacement of septal and posterior tricuspid leaflets, resulting in atrialization of the right ventricle. We report a case of EA in which the etiology of a malfunctioning prosthetic tricuspid valve is depicted on cardiac computed tomography to be as a result of thrombus lodged in the valve.
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http://dx.doi.org/10.4330/wjc.v4.i7.240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421138PMC
July 2012

Cardiac MR imaging of nonischemic cardiomyopathies: imaging protocols and spectra of appearances.

Radiology 2012 Feb;262(2):403-22

Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.

Recent technologic advances in cardiac magnetic resonance (MR) imaging have resulted in images with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MR is a valuable imaging technique for detection and assessment of the morphology and functional characteristics of the nonischemic cardiomyopathy. It has gained acceptance as a standalone imaging modality that can provide further information beyond the capabilities of traditional modalities such as echocardiography and angiography. Black-blood fast spin-echo MR images allow morphologic assessment of the heart with high spatial resolution, while T2-weighted MR images can depict acute myocardial edema. Contrast material-enhanced images can depict and be used to quantify myocardial edema, infiltration, and fibrosis. This review presents recommended cardiac MR protocols for and the spectrum of imaging appearances of the nonischemic cardiomyopathies.
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http://dx.doi.org/10.1148/radiol.11100284DOI Listing
February 2012

Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide.

Clin Ther 2012 Jan 9;34(1):91-100. Epub 2011 Dec 9.

HF Unit, St Vincent's University Hospital, Elm Park, Dublin, Ireland.

Background: The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.

Objectives: This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers.

Methods: Fifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups).

Results: Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01).

Conclusions: Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted.
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http://dx.doi.org/10.1016/j.clinthera.2011.11.002DOI Listing
January 2012

Quantification of mitral regurgitation on cardiac computed tomography: comparison with qualitative and quantitative echocardiographic parameters.

J Comput Assist Tomogr 2011 Sep-Oct;35(5):625-30

Department of Cardiology, St. Vincent's University Hospital, Dublin, Ireland.

Purpose: To assess whether cardiac computed tomographic angiography (CCTA) can quantify the severity of chronic mitral regurgitation (MR) compared to qualitative and quantitative echocardiographic parameters.

Materials And Methods: Cardiac computed tomographic angiography was performed in 23 patients (mean ± SD age, 63 ± 16 years; range, 24-86 years) with MR and 20 patients without MR (controls) as determined by transthoracic echocardiography. Multiphasic reconstructions (20 data sets reconstructed at 5% increments of the electrocardiographic gated R-R interval) were used to analyze the mitral valve. Using CCTA planimetry, 2 readers measured the regurgitant mitral orifice area (CCTA ROA) during systole. A qualitative echocardiographic assessment of severity of MR was made by visual assessment of the length of the regurgitant jet. Quantitative echocardiographic measurements included the vena contracta, proximal isovelocity surface area, regurgitant volume, and estimated regurgitant orifice (ERO). Comparisons were performed using the independent t test, and correlations were assessed using the Spearman rank test.

Results: All controls and the patients with MR were correctly identified by CCTA. For patients with mild, moderate, or severe MR, mean ± SD EROs were 0.16 ± 0.03, 0.31 ± 0.08, and 0.52 ± 0.03 cm² (P < 0.0001) compared with mean ± SD CCTA ROAs 0.09 ± 0.05, 0.30 ± 0.04, and 0.97 ± 0.26 cm² (P < 0.0001), respectively. When echocardiographic measurements were graded qualitatively as mild, moderate, or severe, strong correlations were seen with CCTA ROA (R = 0.89; P < 0.001). When echocardiographic measurements were graded quantitatively, the vena contracta and the ERO showed modest correlations with CCTA ROA (0.48 and 0.50; P < 0.05 for both). Neither the proximal isovelocity surface area nor the regurgitant volume demonstrated significant correlations with CCTA ROA.

Conclusions: Single-source 64-slice CCTA provides a strong agreement with qualitative echocardiographic parameters but only a moderate correlation with quantitative echocardiographic parameters of chronic MR. Cardiac computed tomographic angiography slightly overestimates mild MR while slightly underestimating severe MR.
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http://dx.doi.org/10.1097/RCT.0b013e31822d28b8DOI Listing
December 2011

Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?

Eur J Heart Fail 2011 Oct 30;13(10):1087-95. Epub 2011 Jun 30.

UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

Aims: Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.

Methods And Results: This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction  (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction  was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.

Conclusion: These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.
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http://dx.doi.org/10.1093/eurjhf/hfr079DOI Listing
October 2011

Varicella infection and the impact of late entry into the Irish healthcare system.

J Infect Public Health 2010 23;3(3):106-12. Epub 2010 Aug 23.

Department of Infectious Diseases, St. James's Hospital, Dublin 8, Ireland.

We present a case which highlights several areas of concern relating to the prevention and management of varicella in Ireland. We review the pathophysiology of this virus and highlight its greater potential for morbidity in certain groups, most particularly adult males. The experience and opinions with regard to varicella vaccination in the US and other temperate countries is reviewed along with evidence of changing epidemiology of varicella infection. The National Immunisation Advisory Committee (NIAC) guidelines are reviewed in the context of our experience.
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http://dx.doi.org/10.1016/j.jiph.2010.07.001DOI Listing
December 2010

Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

Eur Radiol 2010 Aug 23;20(8):1886-95. Epub 2010 Mar 23.

Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland.

Objective: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE).

Methods: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis.

Results: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +/- 7 mm vs. 22 +/- 4 mm, P < 0.02) and thickness (3.0 +/- 1 mm vs. 2.2 +/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with/without MV prolapse were detected in MV tent area (-1.0 +/- 0.6 mm vs. 1.3 +/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +/- 0.3 mm vs. 0.8 +/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +/- 19.1 degrees vs. 22.9 +/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +/- 35.5 degrees vs. 22.9 +/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%.

Conclusion: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.
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http://dx.doi.org/10.1007/s00330-010-1760-4DOI Listing
August 2010

Coronary ostial involvement in acute aortic dissection: detection with 64-slice cardiac CT.

Clin Imaging 2009 Nov-Dec;33(6):471-3

Department of Radiology, Cardiac CT/MRI Program, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

A 41-year-old man collapsed after lifting weights at a gym. Following admission to the emergency department, a 64-slice cardiac computed tomography (CT) revealed a Stanford Type A aortic dissection arising from a previous coarctation repair. Multiphasic reconstructions demonstrated an unstable, highly mobile aortic dissection flap that extended proximally to involve the right coronary artery ostium. Our case is an example of the application of electrocardiogram-gated cardiac CT in directly visualizing involvement of the coronary ostia in acute aortic dissection, which may influence surgical management.
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http://dx.doi.org/10.1016/j.clinimag.2009.03.010DOI Listing
January 2010

Accessory left atrial diverticulae: contractile properties depicted with 64-slice cine-cardiac CT.

Int J Cardiovasc Imaging 2010 Feb 19;26(2):241-8. Epub 2009 Sep 19.

Departments of Radiology, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

To assess the contractility of accessory left atrial appendages (LAAs) using multiphasic cardiac CT. We retrospectively analyzed the presence, location, size and contractile properties of accessory LAAs using multiphasic cardiac 64-slice CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar reformats were used to create image planes in axial oblique, sagittal oblique and coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm, axial and sagittal diameters and appendage volumes were recorded in atrial diastole and systole. Regression analysis was performed to assess which imaging appearances best predicted accessory appendage contractility. Twenty-three (23%) patients demonstrated an accessory LAA, all identified along the anterior LA wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All appendages (>or=10 mm) demonstrated significant contraction during atrial systole (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD-contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in atrial diastole was 468.4 +/- 493 mm(3) and in systole was 171.2 +/- 122 mm(3), indicating a mean change in volume of 297.2 +/- 390 mm(3), P < 0.0001. Stepwise multiple regression analysis revealed SOL to be the strongest independent predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties on cardiac CT. Those accessory LAAs with a large sagittal height or depth should be evaluated for contractile properties, and if present should be examined for ectopic activity during electrophysiological studies.
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http://dx.doi.org/10.1007/s10554-009-9511-9DOI Listing
February 2010

Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover.

Eur J Heart Fail 2009 Feb;11(2):191-7

Heart Failure Unit, School of Medicine and Medical Science, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

Aims: Heart failure with preserved ejection fraction (HF-PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF-PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF-PEF and DD.

Methods And Results: We included 85 Caucasian treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all). Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for predicting HF-PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity.

Conclusion: Markers of collagen turnover identify patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF-PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.
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http://dx.doi.org/10.1093/eurjhf/hfn036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639413PMC
February 2009

Long-term safety and efficacy of ivabradine in patients with chronic stable angina.

Cardiology 2007 21;108(4):387-96. Epub 2007 Sep 21.

Fundación Hospital Alcorcon, Alcorcon, Madrid, Spain.

Objective: To assess the long-term safety and antianginal efficacy of two doses of ivabradine, a novel selective and specific inhibitor of the sinus node I(f) current.

Methods: In a randomized double-blind, parallel-group study 386 patients with chronic stable angina were randomized to either ivabradine 5 mg b.i.d. (n = 198, group 1) or ivabradine 7.5 mg b.i.d. (n = 188, group 2) for 12 months. Concomitant medication included antithrombotic agents, lipid-lowering agents, long-acting nitrates and dihydropyridine calcium antagonists. Safety was assessed on the basis of reported adverse events at 1, 3, 6, 9 and 12 months. Antianginal efficacy was based on the reduction in the weekly number of angina attacks and in the consumption of short-acting nitrates from month 0 (baseline) to month 12.

Results: Ivabradine was well tolerated. Phosphene-like mild transient visual symptoms were the most frequently reported adverse events but led to treatment withdrawal in only 4 patients. Resting heart rate was reduced by 9 bpm in group 1 and 12 bpm in group 2. Sinus bradycardia caused treatment withdrawal in only three cases. The QTc (Bazett) interval did not increase. At month 12 relative to month 0 there was a significant reduction in the number of angina attacks per week.

Conclusion: Ivabradine at the recommended doses of 5 and 7.5 mg b.i.d. was well tolerated and demonstrated antianginal efficacy in patients with documented coronary artery disease treated with concomitant antianginal medications.
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http://dx.doi.org/10.1159/000108387DOI Listing
January 2008

Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction.

Circulation 2007 Feb 5;115(7):888-95. Epub 2007 Feb 5.

Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

Background: The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF.

Methods And Results: We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive-like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I (P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001).

Conclusions: These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.106.638569DOI Listing
February 2007