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1.
J Proteomics ; : 104018, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33075551

RESUMO

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and impaired myocardial function. Endomyocardial biopsies (EMB) enable immunohistochemical and molecular characterization of this disease. However, knowledge about specific molecular patterns and their relation to cardiac function in both ventricles is rare. Therefore, we performed a mass spectrometric analysis of 28 paired EMBs of left (LV) and right ventricles (RV) of patients with DCM or suspected myocarditis allowing quantitative profiling of 743 proteins. We analysed associations between protein abundance of LV and RV as well as the echocardiographic parameters LVEF, TAPSE, LVEDDI, and RVEDDI by linear regression models. Overall, more LV than RV proteins were associated with LV parameters or with RVEDDI. Most LV and RV proteins increasing in level with impairing of LVEF were annotated to structural components of cardiac tissue. Additionally, a high proportion of LV proteins with metabolic functions decreased in level with decreasing LVEF. Results were validated with LV heart sections of a genetic murine heart failure model. The study shows, that remodelling and systolic dysfunction in DCM is mirrored by distinct alterations in protein composition of both ventricles. Loss of LV systolic function is reflected predominantly by alterations in proteins assigned to metabolic functions in the LV whereas structural remodelling was more obvious in the RV. Alterations related to intermediate filaments were seen in both ventricles and highlight such proteins as early indicators of LV loss of function. SIGNIFICANCE: The present study report protein sets in the RV and the LV being associated with ventricular function and remodelling in DCM. Protein abundances in the LV and the RV emphasize and expand current knowledge on pathophysiological changes in heart failure and DCM. While RV and LV EMBs do not differ concerning diagnostic assessment of inflammatory status and virus persistence, additional information reflecting disease severity associated protein alterations can be gained by EMB protein profiling. RV and LV protein data provided complementary information. The protein pattern of the LV reflects metabolic changes and an impaired energy production, which is associated with the degree of LV systolic dysfunction and remodelling and may yield important information about the disease status in DCM. On the other hand, at this disease stage of DCM with still preserved RV function, RV alterations in structural proteins may reflect myocardial compensatory protective mechanisms for maintenance of structure and cellular function. The study highlight particular proteins being of interest as heart failure biomarkers in both ventricles which seem to reflect the severity of the disease. Further comparative studies between different HF aetiologies have to evaluate those proteins as markers specific for DCM.

2.
Eur Respir J ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859673

RESUMO

BACKGROUND: Early discharge of patients with acute low-risk pulmonary embolism (PE) requires validation by prospective trials with clinical and quality of life outcomes. METHODS: The multinational Home Treatment of Pulmonary Embolism (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to three-month recurrence (primary outcome) and one-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life [PEmb-QoL] questionnaire) and generic (five-level five-dimension EuroQoL [EQ-5D-5L] scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale [ACTS]) after PE. RESULTS: The primary efficacy outcome occurred in three (0.5%; upper 95.0% CI 1.3%) patients. One-year mortality was 2.4%. The mean PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. EQ-5D-5L was 0.89±0.12 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age, with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 at 3 months (p<0.0001). CONCLUSIONS: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk PE. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.

5.
Clin Res Cardiol ; 109(5): 539-548, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31401672

RESUMO

AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

6.
Eur Heart J ; 41(4): 509-518, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31120118

RESUMO

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

7.
Clin Res Cardiol ; 108(7): 772-778, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30564950

RESUMO

INTRODUCTION: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. METHODS: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV. RESULTS: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. CONCLUSIONS: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae.


Assuntos
Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Recuperação de Função Fisiológica , Tenecteplase/uso terapêutico , Terapia Trombolítica/métodos , Função Ventricular Direita/fisiologia , Doença Aguda , Progressão da Doença , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Circulation ; 139(10): 1249-1258, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586755

RESUMO

BACKGROUND: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. METHODS: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. RESULTS: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. CONCLUSIONS: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Coração Auxiliar , Balão Intra-Aórtico , Infarto do Miocárdio/terapia , Revascularização Miocárdica , Choque Cardiogênico/terapia , Idoso , Fármacos Cardiovasculares/efeitos adversos , Europa (Continente) , Feminino , Coração Auxiliar/efeitos adversos , Humanos , Balão Intra-Aórtico/efeitos adversos , Balão Intra-Aórtico/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Revascularização Miocárdica/efeitos adversos , Revascularização Miocárdica/mortalidade , Desenho de Prótese , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
9.
Clin Hemorheol Microcirc ; 70(4): 381-389, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30320566

RESUMO

BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to induce potent cardioprotection in individuals experiencing coronary ischemia. A protocol combining limb ischemia and electronic muscle stimulation of the ischemic skeletal muscle (RIPC+), performed in advance of coronary artery occlusion, was superior in terms of infarct size reduction when compared to RIPC alone. METHODS: This study was performed to evaluate the benefit of RIPC + in humans compared to a standard RIPC protocol and a control group. Patients with a single vessel coronary artery disease undergoing elective PCI were eligible to participate in this study. ST-segment elevations from an intracoronary ECG during 3 brief episodes of coronary artery balloon occlusions/dilatation were used as the primary endpoint. RESULTS: ST-elevations significantly declined from the first to the third angioplasty in the control but remained at the same level in the RIPC and RIPC+groups. The RIPC group was characterized by the lowest ST-segment shift during coronary ischemia, which was comparable to coronary balloon occlusion number 3 in the control group, indicating successful preconditioning by the conventional RIPC method. In contrast, ST segment elevations were significantly higher in the RIPC + group. Troponin levels taken 24 h after the study procedure were significantly lower in the RIPC when compared to the control and the RIPC + group. CONCLUSION: Our results again confirm the feasibility of remote ischemic preconditioning in patients undergoing coronary angioplasty. According to our results ischemia combined with electronic skeletal muscle stimulation was not superior to conventional RIPC cycles (skeletal muscle ischemia alone).


Assuntos
Precondicionamento Isquêmico/métodos , Extremidade Inferior/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/métodos , Idoso , Feminino , Humanos , Extremidade Inferior/patologia , Masculino
10.
Int J Cardiol ; 270: 278-286, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30082120

RESUMO

BACKGROUND: Myeloid differentiation factor-2 (MD-2) has been shown to be an important modulator of the innate immune system, but its role in cardiac diseases is unknown. We investigated whether MD-2 plays a role as risk predictor and contributor in dilated cardiomyopathy (DCM). METHODS AND RESULTS: We included 174 patients with reduced left ventricular (LV) ejection fraction (LVEF <45%) due to DCM. Coronary artery disease and severe valvular diseases were excluded in all patients by angiography or echocardiography. Cardiac inflammation, viral infection and MD-2 expression were analyzed from right ventricular endomyocardial biopsies. MD-2 was quantified by ELISA in serum upon first hospital admission. Myocyte contractility and inflammatory response after stimulation with recombinant MD-2 protein were analyzed in isolated rat cardiomyocytes. Median follow-up of the patients was 3.51 years (2.73; 4.48) with 34 deaths. Absolute mortality risk increases in patients displaying a MD-2 serum concentration greater than the median (302 ng/ml) was 23% (P < 0.0001). Age- and sex-adjusted Cox regression analyses demonstrated that mortality risk was highly related to MD-2 concentrations (P < 0.001), but not to age or sex. An increase of 100 ng/ml in the MD-2 level was associated with an absolute mortality risk increase of 50.4%. Receiver operating characteristic (ROC) analyses showed no difference between MD-2 and nterminal-pro brain natriuretic peptide (NT-pro-BNP), while the combination of both MD-2 and NT-pro-BNP resulted in a significantly increased capability of risk prediction when compared to NT-pro-BNP alone (P = 0.014). In-vitro, recombinant MD-2 decreases cell shortening and modulates cytokine activation in isolated cardiomyocytes. CONCLUSION: MD-2 predicts long-term outcome in DCM patients and improves mortality risk prediction capability compared to NT-pro-BNP alone. In addition, MD-2 exerts direct negative inotropic effects on isolated cardiomyocytes in-vitro. Further randomized trials should confirm MD-2 as a diagnostic and therapeutic target.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/metabolismo , Antígeno 96 de Linfócito/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Biomarcadores/metabolismo , Cardiomiopatia Dilatada/mortalidade , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Antígeno 96 de Linfócito/farmacologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Valor Preditivo dos Testes , Ratos , Sistema de Registros , Estudos Retrospectivos
11.
Thromb Haemost ; 117(12): 2425-2434, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29212130

RESUMO

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.


Assuntos
Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hemorragia/epidemiologia , Heparina/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Doença Aguda , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Feminino , Seguimentos , Alemanha/epidemiologia , Heparina/efeitos adversos , Humanos , Masculino , Estudos Prospectivos , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/mortalidade , Recidiva , Padrões de Referência , Projetos de Pesquisa , Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
BMC Res Notes ; 10(1): 311, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28854963

RESUMO

BACKGROUND: Vasculitides are commonly unrecognized causes of coronary stenosis and myocardial ischemia. We report on a 24-year old patient with Takayasu's arteritis who underwent urgent percutaneous coronary intervention, suffered from symptomatic restenosis of the left main coronary artery during standard immunosuppressive therapy. CASE PRESENTATION: A 24-year old woman was referred for coronary angiography because of typical progressive angina pectoris. On bicycle ergometry, there were both reproducible symptoms and deep ST segment depressions on precordial leads. Semi-selective angiography of the left coronary artery revealed high-grade ostial stenosis. Because of persistent angina pectoris and electrocardiographic signs of acute myocardial ischemia, immediate percutaneous coronary angioplasty with subsequent implantation of an everolimus-eluting stent was performed. This intervention was performed with excellent angiographic results. Because of several concomitant criteria including hypoechogenicity on postprocedural intravascular ultrasonography, the diagnosis of Takayasu's disease was made. The patient was treated with prednisolone and cyclophosphamide for 5 months. Because of recurrent angina pectoris, another coronary angiography was performed, which revealed high-grade in-stent-restenosis. Immunomodulatory therapy was switched to high-dose prednisolone and the anti-IL-6 receptor antagonist tocilizumab. The high-grade in-stent-restenosis persisted, and aortocoronary bypass graft surgery was performed with two saphenous vein grafts to the left anterior descending and circumflex artery. Since then, the patient has been doing well for 2 years. CONCLUSION: In cases of treatment refractoriness during standard immunosuppressive therapy, more recently developed biological compounds may offer an alternative strategy.


Assuntos
Revascularização Miocárdica/métodos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/cirurgia , Adulto , Feminino , Humanos , Imunossupressores/farmacologia , Recidiva , Arterite de Takayasu/tratamento farmacológico , Adulto Jovem
14.
Eur Heart J ; 38(39): 2936-2943, 2017 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-28431003

RESUMO

Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. Methods and results: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. Conclusion: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.


Assuntos
Transplante de Medula Óssea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Células da Medula Óssea/efeitos da radiação , Método Duplo-Cego , Feminino , Raios gama , Humanos , Infusões Intralesionais , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Transplante de Células-Tronco/métodos , Células-Tronco/efeitos da radiação , Transplante Autólogo , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia
15.
J Am Coll Cardiol ; 69(12): 1536-1544, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28335835

RESUMO

BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).


Assuntos
Fibrinolíticos/uso terapêutico , Embolia Pulmonar/prevenção & controle , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Tenecteplase , Resultado do Tratamento
16.
J Proteomics ; 150: 121-129, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27616206

RESUMO

Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential biomarker is available to predict improvement of cardiac function after therapy accurately. This shotgun proteome study aims to disclose the differences in the endomyocardial proteome between patients with improved LVEF after IA/IgG (responders) and those without improvement (non-responders) before therapy start. Comparative analysis revealed 54 differentially abundant proteins that were mostly confined to carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these proteins revealed highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA/IgG therapy. SIGNIFICANCE: We evaluated the differences in the myocardial proteome of responder and non-responder DCM patients before immunoadsorption therapy and identified a number of differentially abundant proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results. Proteins S100-A8, perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption therapy treatment.


Assuntos
Autoanticorpos/isolamento & purificação , Cardiomiopatia Dilatada/terapia , Técnicas de Imunoadsorção , Miocárdio/metabolismo , Proteoma/análise , Proteômica/métodos , Adulto , Biomarcadores/metabolismo , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia , Projetos Piloto , Prognóstico , Proteoma/metabolismo , Estudos Retrospectivos , Resultado do Tratamento
17.
Clin Res Cardiol ; 105(12): 1030-1041, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27378612

RESUMO

BACKGROUND: In myocardial infarction without cardiogenic shock (CS), the affected coronary vessel has significant influence on the final infarct size and patient prognosis. CS data on this relation are scarce. The objective of this study was to determine the prognostic relevance of the culprit lesion location in patients with CS complicating acute myocardial infarction. METHODS: In the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial patients with CS were randomized to therapy with intraaortic balloon pump or control. Additional CS patients not eligible for the randomized trial were included in a registry. We compared the location of the culprit lesions in these patients with regard to the affected coronary vessel [left main (LM), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA)] and location within the vessel (proximal, mid or distal) regarding short- and long-term outcome. RESULTS: Of 758 patients, the majority had the culprit lesion in the LAD (44 %) compared to RCA (27 %), LCX (19 %) or LM (10 %). Proximal lesions were more frequent than mid or distal culprit lesions (60 vs. 27 vs. 13 %, p < 0.001). No differences were observed for mortality with respect to either culprit vessel (log-rank p value = 0.54). In contrast, a higher mortality was observed for patients with distal culprit lesions after 1 year (log-rank p value = 0.04). This difference persisted after multivariable adjustment (hazard ratio for distal lesions 1.40; 95 % confidential interval 1.03-1.90; p = 0.03). CONCLUSION: For patients with CS complicating myocardial infarction, the culprit vessel seems to be unrelated with mortality whereas distal culprit lesions may have a worse outcome.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Balão Intra-Aórtico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Choque Cardiogênico/terapia , Idoso , Distribuição de Qui-Quadrado , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Balão Intra-Aórtico/efeitos adversos , Balão Intra-Aórtico/mortalidade , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
Basic Res Cardiol ; 111(5): 53, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27412778

RESUMO

Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.


Assuntos
Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/terapia , Imunoglobulina G/uso terapêutico , Adulto , Feminino , Humanos , Técnicas de Imunoadsorção , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Projetos Piloto , Proteômica , Transcriptoma
19.
Thromb Haemost ; 116(1): 191-7, 2016 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-27010343

RESUMO

Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/uso terapêutico , Administração Oral , Inibidores do Fator Xa/administração & dosagem , Serviços de Assistência Domiciliar , Humanos , Alta do Paciente , Estudos Prospectivos , Qualidade de Vida , Recidiva , Fatores de Risco , Rivaroxabana/administração & dosagem , Autoadministração
20.
Dtsch Arztebl Int ; 113(3): 40, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26857515
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