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1.
Eur Heart J ; 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31004144

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD). METHODS AND RESULTS: Evaluation of endomyocardial biopsies from patients with HFpEF (n = 14) revealed that a reduced cardiac PAR2 expression was associated with aggravated DD and increased myocardial fibrosis (r = -0.7336, P = 0.0028). In line, 1-year-old PAR2-knockout (PAR2ko) mice suffered from DD with preserved systolic function, associated with an increased age-dependent α-smooth muscle actin expression, collagen deposition (1.7-fold increase, P = 0.0003), lysyl oxidase activity, collagen cross-linking (2.2-fold increase, P = 0.0008), endothelial activation, and inflammation. In the absence of PAR2, the receptor-regulating protein caveolin-1 was down-regulated, contributing to an augmented profibrotic PAR1 and transforming growth factor beta (TGF-ß)-dependent signalling. This enhanced TGF-ß/PAR1 signalling caused N-proteinase (ADAMTS3) and C-proteinase (BMP1)-related increased collagen I production from cardiac fibroblasts (CFs). PAR2 overexpression in PAR2ko CFs reversed these effects. The treatment with the PAR1 antagonist, vorapaxar, reduced cardiac fibrosis by 44% (P = 0.03) and reduced inflammation in a metabolic disease model (apolipoprotein E-ko mice). Patients with HFpEF with upstream PAR inhibition via FXa inhibitors (n = 40) also exhibited reduced circulating markers of fibrosis and DD compared with patients treated with vitamin K antagonists (n = 20). CONCLUSIONS: Protease-activated receptor 2 is an important regulator of profibrotic PAR1 and TGF-ß signalling in the heart. Modulation of the FXa/FIIa-PAR1/PAR2/TGF-ß-axis might be a promising therapeutic approach to reduce HFpEF.

2.
J Clin Transl Hepatol ; 6(2): 161-167, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29951361

RESUMO

Whereas statistical association of hepatitis C virus (HCV) infection with cardiomyopathy is long known, establishment of a causal relationship has not been achieved so far. Patients with advanced heart failure (HF) are mostly unable to tolerate interferon (IFN)-based treatment, resulting in limited experience regarding the possible pathogenic role of HCV in this patient group. HCV infection often triggers disease in a broad spectrum of extrahepatic organs, with innate immune and autoimmune pathogenic processes involved. The fact that worldwide more than 70 million patients are chronically infected with HCV illustrates the possible clinical impact arising if cardiomyopathies were induced or aggravated by HCV, resulting in progressive HF or severe arrhythmias. A novel path has been opened to finally resolve the long-standing question of cause-effect relationship between HCV infection and cardiac dysfunction, by the recent development of IFN-free, highly efficient, and well tolerable anti-HCV regimens. The new direct-acting antiviral (DAA) agents are highly virus-specific and lack unspecific side-effects upon cardiac function which have always confounded the interpretation of IFN treatment data. The actual frequency of unexplained HF in chronic HCV infection will be determined from a planned large-scale study. Whereas such patients probably constitute a rather small fraction of all those harboring HCV, they have major clinical relevance. It is not yet known which fraction of these patients will significantly benefit from HCV eradication, but this issue will be addressed now in a prospective study.

3.
Heart Rhythm ; 15(1): 3-8, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29304951

RESUMO

BACKGROUND: Percutaneous catheter-based left atrial appendage closure (LAAC) is a procedure being increasingly performed in patients with atrial fibrillation and high bleeding risk. OBJECTIVE: The purpose of this study was to evaluate the incidence of magnetic resonance imaging (MRI)-detected acute brain lesions (ABLs) as well as potential changes in neurocognitive function after percutaneous LAAC in patients with atrial fibrillation. METHODS: Brain MRI at 3 T was performed within 24 hours before and after LAAC along with neurologic (National Institutes of Health Stroke Scale [NIHSS] score) and cognitive (Montreal Cognitive Assessment [MoCA] test) assessment. Acquired MRI sequences included high-resolution diffusion-weighted imaging as well as fluid-attenuated inversion recovery. RESULTS: Successful device implantation was achieved in all 23 patients (age 74.1 ± 10.5 years; 16 male) using the Amulet (n = 18), Occlutech (n = 3), or LAmbre (n = 2) device. Thirty-seven ABLs were detected by MRI in 12 of 23 patients (52%) after LAAC. The number of periprocedural LAA angiographies was significantly higher in patients with ABL than in those without ABL (1.67 ± 0.65 vs 1.18 ± 0.41; P = .048) and was associated with a higher number of ABL (ρ = 0.615; P = .033). Compared to pre-LAAC assessment, post-LAAC MoCA and NIHSS scores revealed similar results. After LAAC, MoCA test (mean 24.1 ± 4.6 vs 23.2 ± 4.6; P = .09) and NIHSS score (mean 1.0 ± 1.7 vs 1.2 ± 1.8; P = .1) were similar between patients with and those without ABL, respectively. CONCLUSION: MRI-detected ABLs are commonly observed after percutaneous LAAC. The number of LAA angiographies is significantly associated with the number of ABLs; however, the clinical implications of ABL have yet to be determined.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Encéfalo/patologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Imagem de Difusão por Ressonância Magnética/métodos , Dispositivo para Oclusão Septal/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Doença Aguda , Idoso , Angiografia , Fibrilação Atrial/complicações , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Complicações Pós-Operatórias , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
4.
Eur J Heart Fail ; 20(3): 460-470, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28891228

RESUMO

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with myocardial remodelling including severe pro-fibrotic changes contributing to an increase in left ventricular stiffness and diastolic dysfunction. Serum C-terminal propeptide of procollagen type I (PIP) strongly correlates with the turnover of extracellular cardiac matrix proteins and fibrosis. Torasemide, but not furosemide, was described to reduce collagen type I synthesis in clinically unstable patients with heart failure with reduced ejection fraction. We evaluated whether its effect translated to HFpEF patients with type 2 diabetes mellitus (T2DM) and abnormal basal PIP levels. METHODS AND RESULTS: We performed a relatively small, single-centre, randomised, double-blind, two-arm parallel-group, active controlled clinical trial in 35 HFpEF patients with T2DM to determine the effects of a 9-month treatment with torasemide vs. furosemide on changes of serum PIP levels. Patients with increased PIP levels (≥110 ng/mL), or evidence of structural changes with a left atrial volume index (LAVI) >29 mL/m2 and abnormal PIP levels (≥70 ng/mL), were eligible to participate. Fifteen patients were female (42%), mean age was 69 years, body mass index was 34.7 kg/m2 , 83% were in New York Heart Association class II/III. Echocardiographic characteristics showed a mean left ventricular ejection fraction of >60%, a left ventricular mass index >120 g/m2 , an E/e' ratio of 14, and a LAVI of 40 mL/m2 with a NT-proBNP of 174 ng/L and a 6-minute walk distance of 421 m. Mean per cent change in PIP was 2.63 ± 5.68% (±SEM) in torasemide vs. 2.74 ± 6.49% in furosemide (P = 0.9898) treated patients. Torasemide was not superior to furosemide in improving functional capacity, diastolic function, quality of life, or neuroendocrine activation. CONCLUSION: In this hypothesis-generating, mechanistic trial in stable HFpEF patients with T2DM, neither long-term administration of torasemide nor furosemide was associated with a significant effect on myocardial fibrosis, as assessed by serum PIP. Further studies are urgently needed in this field. More specific diuretic and anti-fibrotic treatment strategies in T2DM and/or HFpEF are warranted.

5.
J Interv Cardiol ; 31(1): 83-90, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29193333

RESUMO

OBJECTIVES: The present study aimed to evaluate the outcome and potential limitations of a repeated MitraClip procedure (ReClip). BACKGROUND: The MitraClip procedure has emerged as a treatment option in high surgical risk patients suffering from severe mitral regurgitation (MR). However, despite successful initial repair a significant number of patients develops severe recurrent MR. METHODS: Patients undergoing a ReClip procedure in our institution were retrospectively identified. Baseline data and the procedural outcome were assessed to identify potential limitations of such procedures. RESULTS: Fifteen out of 234 patients undergoing a mitral-valve repair with the MitraClip device (Abbott Vascular) underwent a ReClip due to recurrent MR. In 11 patients, a MR reduction of at least one degree without causing mitral valve stenosis (trans-mitral mean gradient ≥5 mmHg) was achieved by performing a ReClip. After 1 year, two patients developed severe recurrent MR again. Pulmonary artery pressures significantly decreased after the procedure in individuals with successful repair (MR reduction of at least one degree and mitral valve mean gradient <5 mmHg). CONCLUSION: A ReClip procedure may be feasible in patients with recurrent MR but the risk benefit ratio should be carefully balanced against other treatment options.


Assuntos
Insuficiência da Valva Mitral , Complicações Pós-Operatórias , Reoperação/métodos , Idoso , Feminino , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Estudos Retrospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Int J Cardiol ; 243: 374-378, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28536004

RESUMO

BACKGROUND: Up to one third of patients with chronic myocarditis (MC) have preserved left ventricular (LV) ejection fraction (MCpEF). The purpose of this study was to evaluate the role of adding 2D speckle-tracking echocardiography (STE) to cardiac magnetic resonance imaging (cMRI) in the diagnosis of patients with MCpEF. METHODS AND RESULTS: We analyzed 67 patients with suspected MCpEF who underwent endomyocardial biopsy (EMB). Thirty-two patients with confirmed chronic myocardial inflammation by EMB served as study group (MCpEF) and the remaining patients (n=35) served as control group. In all patients, 2D STE and cMRI were performed within 48h before EMB. Patients with MCpEF had significantly lower LV global longitudinal systolic strain (GLS) than controls (GLS: -17.01±2.42% vs. -19.39±3.81%, p<0.001; respectively). In line, an abnormal GLS had adequate diagnostic performance to detect MCpEF (sensitivity, specificity, and accuracy of 82%, 70%, and 76%, respectively), which was superior to cMRI based on the Lake-Louise criteria (sensitivity, specificity, and accuracy 54%, 71%, and 67%, respectively). In addition, adding GLS to the Lake-Louise criteria improved significantly the diagnostic performance of cMRI to detect MCpEF (sensitivity, specificity, and accuracy 96%, 55%, and 75%, respectively). CONCLUSION: The findings of this study suggest that GLS using 2D STE could play an important role in the diagnostic evaluation of patients with suspected chronic myocarditis with preserved LV ejection fraction (MCpEF).


Assuntos
Ecocardiografia/métodos , Imagem Multimodal/métodos , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Adulto , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Cardiovasc Res ; 113(8): 906-914, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28402411

RESUMO

Aim: To address the mechanisms responsible for the increase in LV filling pressures induced by acute hypertension transients in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: Multiple-beat pressure-volume loops were recorded during inferior vena cava occlusion in 39 HFpEF patients and 20 controls during handgrip and atrial pacing. We measured the contribution of relaxation, elastic recoil, and stiffness to instantaneous diastolic pressure using a novel processing method. Fibrosis was quantified from endomyocardial biopsies. HFpEF patients showed higher diastolic pressures and stiffness constant than controls (P < 0.05 for all). As opposed to controls, all intrinsic global diastolic properties were sensitive to acute changes in systolic pressure in the HFpEF group. In fact, the stiffness constant increased by more than 50% during handgrip in HFpEF patients (P < 0.05), tightly related to changes in systolic pressure (fixed-effect = 0.26 mm Hg per mm Hg [95% CI = 0.15-0.37]; P < 0.0001). Incomplete relaxation contributed to increasing pressure before atrial contraction, but changes in end-diastolic pressure was mostly caused by the increase in stiffness. The degree of pressure-sensitivity of stiffness correlated with myocardial collagen volume and crosslinking (R = 0.40 to 0.82 for all). Conclusion: Acute chamber stiffening is the main mechanism responsible for rising late-diastolic pressures when HFpEF patients undergo hypertension transients. This stiffening behaviour is related to impaired dynamic systolic-diastolic interactions and correlates with matrix remodelling. Ventricular-vascular relationships are a promising target in HFpEF and should be taken into account when assessing diastolic function.


Assuntos
Diástole/fisiologia , Hipertensão/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Feminino , Força da Mão/fisiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia
9.
Clin Res Cardiol ; 106(7): 551-556, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28236021

RESUMO

AIMS: Hepatitis C virus (HCV) has been associated with cardiomyopathies. Former anti-HCV therapies employing interferon could have serious side effects in patients with advanced heart failure since interferon may adversely impact upon cardiac function. We, therefore, examined whether the novel, interferon-free and highly virus-selective anti-HCV combination therapy might be applicable even in advanced or end-stage heart failure. METHODS AND RESULTS: In a retrospective series of HCV-positive patients admitted to our institution with suspected cardiac disease, coronary, valvular or hypertensive heart disease was diagnosed in 70/146 (47.9%). Among the others, 36/76 (47.4%) had myocardial disease: LV (32.9%)/RV (13.2%) hypertrophy, RV dysfunction (13.2%)/dilation (6.6%), severe diastolic dysfunction (7.9%), pulmonary hypertension (22.4%). One critically ill patient listed for heart transplantation (HTX) had previously not tolerated an interferon-based protocol. To still improve her chance of enduring transplant survival, we attempted an interferon-free virus-selective antiviral combination drug protocol under careful monitoring of possible side effects. Regarding clinical status she tolerated this treatment well, with the exception of transient severe hyponatremia requiring substitution. Her NYHA functional class improved from II-IV before to class II immediately after successful complete HCV elimination. CONCLUSIONS: Whereas prevalence of cardiac dysfunction and potential benefit from antiviral treatment was reported previously, there is lack of data regarding the response of patients with advanced heart failure. Since the highly HCV-selective drugs used above do not eliminate other cardiotropic viruses and have no direct effect on inflammation, massive improvement in such critically ill patients indicates a causal role of HCV in their cardiac failure, and of HCV elimination in their functional recovery.


Assuntos
Implantes Absorvíveis , Antivirais/uso terapêutico , Doença da Artéria Coronariana/cirurgia , Hepatite C Crônica/tratamento farmacológico , Tecidos Suporte , Idoso , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , DNA Viral/análise , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Incidência , Imagem Cinética por Ressonância Magnética , Masculino , Estudos Retrospectivos
11.
Nat Commun ; 7: 13710, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27966531

RESUMO

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-ß2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-ß2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.


Assuntos
Aminoácido Oxirredutases/fisiologia , Insuficiência Cardíaca/metabolismo , Miocárdio/patologia , Aminoácido Oxirredutases/sangue , Aminoácido Oxirredutases/metabolismo , Animais , Fibrose/metabolismo , Humanos , Camundongos Knockout , Miocárdio/metabolismo , Estresse Fisiológico
12.
Artigo em Alemão | MEDLINE | ID: mdl-26830776

RESUMO

CASE REPORT: The case of a 40-year-old woman with paroxysmal symptomatic atrial fibrillation and implanted occluder of a patent foramen ovale (PFO; AMPLATZER™ Septal Occluder, St. Jude Medical) is reported. Due to the symptomic atrial fibrillation, pulmonary vein isolation was planned. METHODS: Under transesophageal, echocardiographic control the transseptal puncture was performed posterior inferior of the occluder without any complications. The pulmonary vein was successfully isolatedusing radiofrequency energy. CONCLUSION: This case demonstrates that transseptal puncture in pulmonary vein isolation with an inserted PFO occluder under additional transesophageal, echocardiographic monitoring is safe and feasible.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Forame Oval Patente/cirurgia , Septos Cardíacos/cirurgia , Dispositivos de Oclusão Vascular , Adulto , Fibrilação Atrial/complicações , Estudos de Viabilidade , Feminino , Forame Oval Patente/complicações , Humanos , Resultado do Tratamento
14.
Clin Res Cardiol ; 104(11): 955-63, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25956143

RESUMO

BACKGROUND: End-diastolic pressure-volume relationship and LV stiffness, key parameter for diagnosing diastolic dysfunction within Heart failure with preserved ejection fraction (HFpEF) patients, can be directly obtained only by invasive pressure-volume (PV) measurements. Therefore, we aimed to establish diastolic pressure-volume quotient (DPVQ), as a new non-invasive parameter for estimation of LV stiffness in HFpEF obtained by 3D echocardiography (3DE) and tissue Doppler imaging. METHODS: Twenty-three HFpEF patients with suspected diastolic dysfunction, scheduled for invasive pressure-volume loop analyses obtained by conductance catheterization were included. PV loop measurements were compared with simultaneous 3DE full-volume recordings of the LV and tissue Doppler measurements for LV diastolic function. LV filling index E/E' was used for estimation of diastolic pressure. Single-beat method was performed to calculate LV stiffness constant (ß SB). RESULTS: Fourteen of twenty-three patients showed increased and 9/23 revealed normal LV stiffness ß. End-diastolic, end-systolic and stroke volume obtained by 3DE correlated with those from PV loop analysis (r = 0.63, r = 0.57 and r = 0.71, respectively). Estimated diastolic pressure and DPVQ correlated with invasive measurements (r = 0.81 and r = 0.91, both p < 0.001). Accordingly, calculated stiffness constant ß SB revealed a significant correlation with invasive determined stiffness coefficient ß (r = 0.73, p < 0.001). DPVQ and ß SB correlated with NT-proBNP plasma level (r = 0.67 and r = 0.58, both, p < 0.001). CONCLUSION: 3D echocardiography allows accurate non-invasive measurements of diastolic pressure-volume quotient which correlates with invasive determined LV stiffness in HFpEF.


Assuntos
Ecocardiografia Tridimensional/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Feminino , Insuficiência Cardíaca/complicações , Humanos , Imagem Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Volume Sistólico , Disfunção Ventricular Esquerda/complicações
15.
ESC Heart Fail ; 2(3): 121-132, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27708854

RESUMO

AIMS: This study aimed to evaluate ventricular diastolic properties using three-dimensional echocardiography and tissue Doppler imaging at rest and during exercise in heart failure with preserved ejection fraction (HFpEF) patients with borderline evidence of diastolic dysfunction at rest. METHODS AND RESULTS: Results obtained from 52 HFpEF patients (left ventricular ejection fraction ≥ 50%) identified on the basis of heart failure symptoms and E/E' values between 8 and 15 were compared with those obtained in 26 control patients with no evidence of cardiovascular disease. Mitral flow patterns, tissue Doppler imaging, and volume analysis obtained by three-dimensional echocardiography were performed at rest and during bicycle exercise. Diastolic compliance was indexed by the E/E' ratio and left ventricular end-diastolic volume [(E/E')/EDV]. There were no significant differences in end-diastolic volume (EDV), stroke volume (SV), or ejection fraction at rest between groups. In 27 of the 52 patients, E/E' increased during exercise (11.2 ± 3.7 to 16.8 ± 10.5), driven by a failure to augment early diastole (E'). This correlated with a fall in SV and was associated with an increase in the diastolic index (E/E')/EDV as a measure for LV stiffness (0.122 ± 0.038 to 0.217 ± 0.14/mL), indicating that impaired diastolic reserve (designated PEF-IDR) contributed to exercise intolerance. Of the 52 patients, 25 showed no changes in E/E' during exercise associated with a significant rise in SV and cardiac output, still inappropriate compared with controls. Despite disturbed early diastole (E'), a blunted increase in estimated systolic LV elastance indicated that impaired systolic reserve and chronotropic incompetence rather than primarily diastolic disturbances contributed to exercise intolerance in this group (designated PEF). CONCLUSION: Three-dimensional stress echocardiography may allow non-invasive analysis of changes in cardiac output that can differentiate HFpEF patients with an inappropriate increase or a fall in SV during exercise. Impaired systolic or diastolic reserve can contribute to these haemodynamic abnormalities, which may arise from different underlying pathophysiologic mechanisms.

17.
Int J Cardiol ; 168(5): 4652-7, 2013 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-23968714

RESUMO

BACKGROUND: Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF. METHODS: 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 µg/l or ferritin of 100-299 µg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies. RESULTS: Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency. CONCLUSION: In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Ferro/deficiência , Volume Sistólico/fisiologia , Função Ventricular Esquerda , Biomarcadores/sangue , Cateterismo Cardíaco , Diástole , Ecocardiografia , Tolerância ao Exercício , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Ferro/sangue , Fatores de Risco , Pressão Ventricular
19.
Mediators Inflamm ; 2013: 875420, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23576857

RESUMO

BACKGROUND: The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. METHODS AND RESULTS: N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, -8.36 ± -3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (-9.4 ± 1.4 versus -16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). CONCLUSION: Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi.


Assuntos
Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Ecocardiografia/métodos , Inflamação/patologia , Miocardite/imunologia , Miocardite/patologia , Adulto , Biópsia , Cardiomiopatias/metabolismo , Feminino , Humanos , Técnicas In Vitro , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Miocardite/metabolismo
20.
Am J Respir Crit Care Med ; 186(2): 181-9, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22561959

RESUMO

RATIONALE: Severe increase in right ventricular pressure can compromise left ventricular (LV) function because of impaired interventricular interaction and aggravate the symptoms. OBJECTIVES: To elucidate how nonsevere idiopathic pulmonary arterial hypertension (IPAH) influences LV function because of impaired interventricular interaction. METHODS: Invasive pressure-volume (PV) loop analysis obtained by conductance catheterization was performed at rest and during atrial pacing in patients with mild IPAH (n = 10) compared with patients with isolated LV diastolic dysfunction (DD) (n = 10) and control subjects without heart failure symptoms (n = 9). MEASUREMENTS AND MAIN RESULTS: Patients with nonsevere IPAH (pulmonary artery pressure mean 29 ± 5 mm Hg) and patients with DD showed preserved systolic (ejection fraction 63 ± 12% and 62 ± 9%) and impaired LV diastolic function at rest (LV stiffness 0.027 ± 0.012 ml(-1) and 0.029 ± 0.014 ml(-1)). During pacing at 120 per minute patients with IPAH and DD decreased their stroke volume (-25% and -30%; P < 0.05) and failed to increase cardiac output significantly. Opposite to patients with DD and control subjects, temporary preload reduction during inferior vena cava occlusion initially induced an expansion of LV end-diastolic volume in IPAH (+7%; P < 0.05), whereas end-diastolic pressure continuously dropped. This resulted in an initial downward shift to the right of the PV loop indicating better LV filling, which was associated with a temporary improvement of cardiac output (+11%; P < 0.05) in the patients with IPAH, but not in patients with DD and control subjects. CONCLUSIONS: Mild idiopathic pulmonary arterial pressure impairs LV diastolic compliance even in the absence of the intrinsic LV disease and contributes to the reduced cardiac performance at stress.


Assuntos
Hipertensão Pulmonar/complicações , Disfunção Ventricular Esquerda/etiologia , Adulto , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Ecocardiografia , Feminino , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
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