Mariano Larman

Universidad de Navarra, Pamplona, Navarre, Spain

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Publications (47)229.71 Total impact

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    ABSTRACT: Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P<0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs (r=0.653, P<0.001; r=0.541, P<0.01) and proteins (r=0.588, P<0.001; r=0.556, P<0.005) in all subjects and with left ventricular end-diastolic wall stress (r=0.450; P<0.05) in patients. Plasma cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased (P<0.001) in patients compared with controls. Plasma cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide (r=0.386; P<0.005), carboxy-terminal propeptide of procollagen type I (r=0.550; P<0.001), and amino-terminal propeptide of procollagen type III (r=0.267; P<0.05) in all subjects. In vitro, cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (P<0.05) and the expression of procollagen type I (P<0.05) and III (P<0.01) mRNAs. These findings show that an excess of cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin.
    Hypertension 12/2013; · 6.87 Impact Factor
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    ABSTRACT: The study is made to describe the efficacy and safety of balloon postdilatation (BPD) for the treatment of residual aortic regurgitation (RAoR) after transcatheter aortic valve implantation (TAVI). A single-center observational study is made with 157 consecutive patients accepted to TAVI. The patients were divided into two groups (no BPD-period and BPD-period). Before BPD, RAoR ≥ 2 was seen in 25% of the patients in group 1 and in 29% of the patients in group 2 (p ≥ 0.593). BPD was carried out in 95% (n = 21) of the patients in group 2 with RAoR ≥ 2. Regurgitation improved one grade in 68% of the cases (n = 15), 2 grades in 14% (n = 3), and remained without change in 18% (n = 4). RAoR < 2 was achieved in 91% (n = 73) of the patients in group 2 versus 75% (n = 58) in group 1 (RR = 0.35, 95% CI 0.16-0.80, p = 0.013). We recorded no aortic ring ruptures, damage to the device or displacements. Slight central regurgitation not present before BPD was registered in one case. BPD offers a very good safety profile and reduces RAoR in a large percentage of cases. BPD should be considered for the treatment of moderate to severe RAoR following TAVI. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2013; · 2.51 Impact Factor
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    ABSTRACT: Although drug-eluting stents have dramatically reduced angiographic restenosis and clinical need for repeat revascularization procedures, some adverse effects, such as late stent thrombosis, have been described. We evaluated clinical performance of paclitaxel-eluting stents coated with a new bioactive polymer system (P-5) based on a copolymer of an acrylic derivative of triflusal in patients with coronary artery disease. This was a multicenter, observational, prospective study to assess the incidence of target lesion revascularization (TLR) at 6 months and clinical major adverse cardiac events (MACEs) at 1 and 6 months and 1 and 2 years post-stent implantation in 537 patients. After stent implantation, only 1 case of thrombus and acute occlusion was reported in 1 lesion (0.14%). The incidence of new TLR was 0.89% at 6 months, 1.08% at 1 year, and 1.49% at 2 years, with a cumulative incidence of 3.54%. MACEs included cardiac death (0.93%), myocardial infarction (0.37%), and cardiac surgery (0.19%). No cases of late or very late stent thrombosis were recorded. Under routine clinical practice, the implantation of paclitaxel-eluting stents coated with P-5 is associated with favorable clinical outcomes in both the short and long term (2 years) in patients with coronary artery disease.
    The Journal of invasive cardiology 08/2013; 25(8):391-6. · 1.57 Impact Factor
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    ABSTRACT: AIMS: We investigated whether the pro-fibrotic matricellular protein osteopontin (OPN) is associated with the enzymes involved in the extracellular synthesis of fibril-forming collagen type I (i.e., procollagen C-proteinase, PCP) and its cross-linking to form insoluble fibrils (i.e., lysyl oxidase, LOX) in heart failure (HF) of hypertensive origin.Methods and ResultsOPN, PCP and LOX were assessed by histochemical and molecular methods in the myocardium of 21 patients with hypertensive heart disease (HHD) and HF. Whereas the myocardial expression of OPN was very scarce in control hearts (N=10), it was highly expressed in HF patients (P<0.0001). OPN was directly correlated with LOX (r=0.460, P=0.041), insoluble collagen (r=0.534, P=0.015), pulmonary capillary wedge pressure (r=0.558; P=0.009) and left ventricular (LV) chamber stiffness (r=0.458, P=0.037), and inversely correlated with LV ejection fraction (r=-0.513, P=0.017) in all patients. OPN did not correlate with PCP and other parameters assessing collagen synthesis by fibroblasts or degradation by matrix metalloproteinases. In vitro studies showed that OPN significantly (P<0.05) increases the expression and activity of LOX in human cardiac and dermal fibroblasts. CONCLUSIONS: An excess of OPN is associated with increased LOX and insoluble collagen, as well as with LV stiffness and systolic dysfunction in patients with HHD and HF. In addition, OPN up-regulates LOX in human fibroblasts. It is suggested that the OPN-LOX axis might facilitate the formation of insoluble collagen (i.e., stiff and resistant to degradation) and the subsequent alteration in LV mechanical properties and function in patients with HHD and HF.
    Cardiovascular research 04/2013; · 5.81 Impact Factor
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    ABSTRACT: We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r=0.639; P<0.001), insoluble stiff collagen (r=0.474; P<0.005), CCL (r=0.625; P<0.001), and LOX (r=0.410; P<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r=0.612; P<0.005), LOX (r=0.538; P<0.01), left ventricular chamber stiffness constant (r=0.535; P<0.005), peak filling rate (r=-0.343; P<0.05), ejection fraction (r=-0.430; P<0.01), and amino-terminal propeptide of brain natriuretic peptide (r=0.421; P<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.
    Hypertension 07/2012; 60(3):677-83. · 6.87 Impact Factor
  • Revista Espa de Cardiologia 01/2011; 64(1):80-2. · 3.20 Impact Factor
  • American Journal of Cardiology - AMER J CARDIOL. 01/2011; 107(8).
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    ABSTRACT: This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis.
    JACC. Cardiovascular Interventions 09/2010; 3(9):911-9. · 1.07 Impact Factor
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    ABSTRACT: In some patients, cardiac contractions cause the coronary artery segment adjacent to a stent to move in such a way that accurate stent positioning is difficult. A number of techniques have been described for immobilizing the stent at the target site by inducing periods of either asystole or tachycardia. This study shows how pulsatile motion can be controlled by means of rapid ventricular pacing via an angioplasty guidewire. The study involved 27 consecutive patients in whom excessive stent movement during angioplasty complicated accurate stent implantation. In these selected patients, myocardial tachycardia was induced by transcoronary ventricular pacing via an angioplasty guidewire with the aim of reducing the pulsatile motion of the stent. At baseline, the median displacement was 4.08 mm (interquartile range 2.75 mm). During pacing at 100 and 150 beats per minute, the median displacement was 1.39 mm and 0.54 mm, respectively (interquartile range 1.66 mm and 0.54 mm, respectively). Transcoronary myocardial pacing was effective in 96% of cases. No complications associated with pacing were reported. Transcoronary ventricular pacing via an angioplasty guidewire was an effective and safe method for achieving stent immobilization in cases where there was excessive pulsatile motion.
    Revista Espa de Cardiologia 04/2009; 62(3):288-92. · 3.20 Impact Factor
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    ABSTRACT: Introduction and objectivesIn some patients, cardiac contractions cause the coronary artery segment adjacent to a stent to move in such a way that accurate stent positioning is difficult. A number of techniques have been described for immobilizing the stent at the target site by inducing periods of either asystole or tachycardia. This study shows how pulsatile motion can be controlled by means of rapid ventricular pacing via an angioplasty guidewire.MethodsThe study involved 27 consecutive patients in whom excessive stent movement during angioplasty complicated accurate stent implantation. In these selected patients, myocardial tachycardia was induced by transcoronary ventricular pacing via an angioplasty guidewire with the aim of reducing the pulsatile motion of the stent.ResultsAt baseline, the median displacement was 4.08 mm (interquartile range, 2.75 mm). During pacing at 100 and 150 beats per minute, the median displacement was 1.39 mm and 0.54 mm, respectively (interquartile range, 1.66 mm and 0.54 mm, respectively). Transcoronary myocardial pacing was effective in 96% of cases. No complications associated with pacing were reported.ConclusionsTranscoronary ventricular pacing via an angioplasty guidewire was an effective and safe method for achieving stent immobilization in cases where there was excessive pulsatile motion.Introducción y objetivosLa contracción cardiaca genera en ocasiones un desplazamiento de la arteria coronaria sobre el stent que puede dificultar su precisa implantación. Se han descrito varias técnicas para inmovilizar el stent en la posición deseada mediante la inducción de periodos tanto de asistolia como de taquicardia. Este estudio muestra cómo este fenómeno de vaivén es controlable mediante la estimulación ventricular eléctrica rápida a través de la guía terapéutica de angioplastia.MétodosSe ha seleccionado de manera consecutive a 27 pacientes en los que durante la angioplastia el excesivo desplazamiento del stent dificultaba su correcta implantación. En los casos seleccionados, se taquicardiza el miocardio mediante estimulación eléctrica ventricular de forma transcoronaria a través de la guía terapéutica para lograr una reducción del desplazamiento en vaivén del stent.ResultadosEl desplazamiento presenta una mediana en situación basal de 4,08 (intervalo intercuartílico, 2,75) mm. Durante la estimulación a 100 y 150 lat/min, el desplazamiento presenta una mediana de 1,39 y 0,54 (intervalos intercuartílicos, 1,66 y 0,54) mm, respectivamente. La estimulación miocárdica transcoronaria ha sido eficaz en el 96% de los casos. No se han observado complicaciones en relación con la estimulación eléctrica.ConclusionesLa estimulación ventricular transcoronaria a través de la guía terapéutica es un método efectivo y seguro para inmovilizar el stent en caso de desplazamiento de vaivén.
    Revista Española de Cardiología (English Edition). 03/2009;
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    ABSTRACT: Introduction and objectives In some patients, cardiac contractions cause the coronary artery segment adjacent to a stent to move in such a way that accurate stent positioning is difficult. A number of techniques have been described for immobilizing the stent at the target site by inducing periods of either asystole or tachycardia. This study shows how pulsatile motion can be controlled by means of rapid ventricular pacing via an angioplasty guidewire. Methods The study involved 27 consecutive patients in whom excessive stent movement during angioplasty complicated accurate stent implantation. In these selected patients, myocardial tachycardia was induced by transcoronary ventricular pacing via an angioplasty guidewire with the aim of reducing the pulsatile motion of the stent. Results At baseline, the median displacement was 4.08 mm (interquartile range 2.75 mm). During pacing at 100 and 150 beats per minute, the median displacement was 1.39 mm and 0.54 mm, respectively (interquartile range 1.66 mm and 0.54 mm, respectively). Transcoronary myocardial pacing was effective in 96% of cases. No complications associated with pacing were reported. Conclusions Transcoronary ventricular pacing via an angioplasty guidewire was an effective and safe method for achieving stent immobilization in cases where there was excessive pulsatile motion.
    Revista Espanola De Cardiologia - REV ESPAN CARDIOL. 01/2009; 62(3):288-292.
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    ABSTRACT: The aim of this study was to investigate whether torasemide modifies collagen cross-linking in the failing human heart. We analyzed the degree of cross-linking and the expression of the enzyme lysyl oxidase, which regulates cross-linking, in the myocardium of patients with chronic heart failure at baseline and after 8 months of treatment with either torasemide or furosemide in addition to their standard heart failure therapy. Whereas lysyl oxidase protein expression was very scarce in normal hearts, it was highly expressed in failing hearts. Cross-linking was increased (P<0.001) in heart failure patients compared with normal hearts. These 2 parameters decreased (P=0.021 and P=0.034) in torasemide-treated patients and remained unchanged in furosemide-treated patients. In addition, more (P=0.009) patients showed normalization of left ventricular chamber stiffness in the torasemide subgroup than in the furosemide subgroup after treatment. Lysyl oxidase expression correlated with cross-linking (r=0.661; P<0.001), and cross-linking correlated with left ventricular chamber stiffness (r=0.452; P=0.002) in all patients. These findings show for the first time that lysyl oxidase overexpression is associated with enhanced collagen cross-linking in the failing human heart. In addition, we report that the ability of torasemide to correct both lysyl oxidase overexpression and enhanced collagen cross-linking results in normalization of left ventricular chamber stiffness in patients with heart failure. Lysyl oxidase may thus represent a target for reduction of stiff collagen and improvement of left ventricular mechanical properties in heart failure patients.
    Hypertension 12/2008; 53(2):236-42. · 6.87 Impact Factor
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    ABSTRACT: This study sought to assess the incidence, predictors, and outcome of drug-eluting stent(DES) thrombosis in real-world clinical practice. The DES thromboses in randomized trials could not be comparable to those observed in clinical practice, frequently including off-label indications. We designed a large-scale, nonindustry-linked multicentered registry, with 20 centers in Spain. The participant centers provided follow-up data for their patients treated with DES, reporting a detailed standardized form in the event of any angiography-documented DES-associated thrombosis occurring. Of 23,500 patients treated with DES, definite stent thrombosis(ST) developed in 301: 24 acute, 125 subacute, and 152 late. Of the late, 62 occurred >1 year(very late ST). The cumulative incidence was 2% at 3 years. Antiplatelet treatment had been discontinued in 95 cases(31.6%). No differences in incidences were found among stent types. Independent predictors for subacute ST analyzed in a subgroup of 14,120 cases were diabetes, renal failure, acute coronary syndrome, ST-segment elevation myocardial infarction, stent length, and left anterior descending artery stenting, and for late ST were ST-segment elevation myocardial infarction, stenting in left anterior descending artery, and stent length. Mortality at 1-year follow-up was 16% and ST recurrence 4.6%. Older age, left ventricular ejection fraction <45%, nonrestoration of Thrombolysis In Myocardial Infarction flow grade 3, and additional stenting were independent predictors for mortality. The cumulative incidence of ST after DES implantation was 2% at 3 years. No differences were found among stent types. Patient profiles differed between early and late ST. Short-term prognosis is poor, especially when restoration of normal flow fails.
    Journal of the American College of Cardiology 04/2008; 51(10):986-90. · 14.09 Impact Factor
  • Revista Espa de Cardiologia 02/2008; 61(1):96-7. · 3.20 Impact Factor
  • Revista Espanola De Cardiologia - REV ESPAN CARDIOL. 01/2008; 61(1):96-97.
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    ABSTRACT: To investigate whether Annexin A5 (AnxA5) is related to hypertensive heart disease (HHD) and whether this relation is dependent of apoptosis. Hypertensives without cardiac abnormalities (stage A), with left ventricular hypertrophy (LVH) (stage B), and with LVH and clinical manifestations of chronic HF (stage C), were studied. AnxA5 was quantified in endomyocardial biopsies by real time RT-PCR, Western blot, and immunohistochemistry, and apoptosis by DNA fragmentation, caspase-3 activation, and PARP and Bax/Bcl-2 ratios. Plasma AnxA5 was measured by ELISA in samples from the coronary sinus and the antecubital vein. Although AnxA5 mRNA did not change, myocardial and plasma AnxA5 were increased in hypertensives stages B and C compared with normotensives and hypertensives stage A. Myocardial AnxA5 was inversely correlated with parameters assessing systolic function in all hypertensives, this association being independent of apoptosis. Myocardial AnxA5 was directly correlated with plasma AnxA5. Plasma AnxA5 was inversely correlated with systolic function in all hypertensives. This cross-sectional study shows that myocardial AnxA5 upregulation is associated with HHD and impairment of systolic function in hypertensive patients, this association being independent of apoptosis. Plasma AnxA5 can be a marker of myocardial AnxA5 upregulation and systolic dysfunction in patients with HHD.
    European Heart Journal 12/2007; 28(22):2785-91. · 14.10 Impact Factor
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    ABSTRACT: To investigate whether the glycoprotein (gp130)-mediated survival pathway, which protects cardiomyocytes from apoptosis, is depressed in left ventricular hypertrophy hypertensive patients with chronic heart failure. Transvenous endomyocardial biopsies were obtained in 52 hypertensive patients with left ventricular hypertrophy: 28 without heart failure and 24 with heart failure. gp130 and gp130-dependent antiapoptotic pathways p42/44 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) as well as gp130 agonist cardiotrophin-1 were analyzed by reverse transcriptase-polymerase chain reaction and western blot. Apoptosis was assessed by DNA end-labeling (TUNEL), caspase-3 immunostaining and caspase substrate poly(ADP-ribose) polymerase cleavage. gp130 protein expression (P < 0.05) and p42/44 MAPK and PI3K/Akt activation (P < 0.01) were decreased in heart-failure hypertensive patients compared with nonheart-failure hypertensive individuals. No changes in gp130 mRNA expression were found between the two groups. Cardiotrophin-1 was increased (P < 0.05) at both the mRNA and protein levels in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Cardiomyocyte apoptosis was increased (P < 0.01) in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Inverse correlations (P < 0.01) occurred between cardiomyocyte apoptosis and p42/44 MAPK and PI3K/Akt activation in all hypertensive patients. Cardiotrophin-1 correlated inversely (r = -0.554, P < 0.05) with gp130 in all hypertensive individuals. In cultured HL-1 cardiomyocytes, cardiotrophin-1 decreased (P < 0.05) the gp130:phosphorylated gp130 (at Ser782) ratio and increased (P < 0.05) gp130ubiquitination. An association exists between depression of the gp130 cytoprotective pathway and stimulation of cardiomyocyte apoptosis in hypertensive patients that develop heart failure. Whether the excess of cardiotrophin-1 induces ligand-induced receptor down-regulation in these patients requires further study.
    Journal of Hypertension 10/2007; 25(10):2148-57. · 4.22 Impact Factor
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    ABSTRACT: This study sought to investigate whether torasemide inhibits the enzyme involved in the myocardial extracellular generation of collagen type I molecules (i.e., procollagen type I carboxy-terminal proteinase [PCP]). Torasemide has been reported to reduce myocardial fibrosis in patients with chronic heart failure (HF). Chronic HF patients received either 10 to 20 mg/day oral torasemide (n = 11) or 20 to 40 mg/day oral furosemide (n = 11) in addition to their standard HF therapy. At baseline and after 8 months from randomization, right septal endomyocardial biopsies were obtained to analyze the expression of PCP by Western blot and the deposition of collagen fibers (collagen volume fraction [CVF]) with an automated image analysis system. The carboxy-terminal propeptide of procollagen type I (PICP) released as a result of the action of PCP on procollagen type I was measured in serum by radioimmunoassay. The ratio of PCP active form to PCP zymogen, an index of PCP activation, decreased (p < 0.05) in torasemide-treated patients and remained unchanged in furosemide-treated patients. A reduction (p < 0.01) in both CVF and PICP was observed in torasemide-treated but not in furosemide-treated patients. Changes in PCP activation were positively correlated (p < 0.001) with changes in CVF and changes in PICP in patients receiving torasemide. These findings suggest the hypothesis that the ability of torasemide to reduce myocardial fibrosis in chronic HF patients is related to a decreased PCP activation. Further studies are required to ascertain whether PCP may represent a new target for antifibrotic strategies in chronic HF.
    Journal of the American College of Cardiology 08/2007; 50(9):859-67. · 14.09 Impact Factor
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    ABSTRACT: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF). Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients. We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay. Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects. These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.
    Journal of the American College of Cardiology 08/2006; 48(1):89-96. · 14.09 Impact Factor
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    ABSTRACT: To investigate whether cardiac expression of the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha) is altered in patients with hypertensive heart disease (HHD). We studied endomyocardial septal biopsies from 24 patients with essential hypertension divided into three groups: 6 without left ventricular hypertrophy (LVH) (HT group), 10 with LVH (LVH group), and 8 with LVH and heart failure (HF) (HF group). The expression of two PPARalpha isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARalpha target genes were evaluated by RT-PCR. Histomorphological features were evaluated in a second myocardial sample from LVH and HF groups. Whereas the expression of native PPARalpha protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPARalpha protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARalpha was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPARalpha target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARalpha protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPARalpha protein was directly correlated with left ventricular volumes, and inversely with ejection fraction in all hypertensives. These findings suggest that post-transcriptional regulation of PPARalpha isoforms is altered in patients with HHD, namely in those developing HF. An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling.
    Cardiovascular Research 04/2006; 69(4):899-907. · 5.81 Impact Factor

Publication Stats

1k Citations
229.71 Total Impact Points

Institutions

  • 2002–2013
    • Universidad de Navarra
      • Division of Cardiovascular Sciences
      Pamplona, Navarre, Spain
    • Hospital Universitario Virgen de la Arrixaca
      • Departamento de Cardiología
      Murcia, Murcia, Spain
  • 1991–2013
    • Policlínica Gipuzkoa
      San Sebastián, Basque Country, Spain
  • 2004
    • University Hospital Donostia
      San Sebastián, Basque Country, Spain