RESUMO
BACKGROUND: Heart transplantation is limited by severe donor organ shortage. Regardless of the changes made in the acceptance of marginal donors, any such mechanism cannot be considered successful unless recipient graft survival rates remain acceptable. A stress echo-driven selection of donors has proven successful in older donors with normal left ventricular resting function and in standard donors with reversible resting left ventricular dysfunction acutely improving during stress, or slowly improving (over hours) during intensive hormonal treatment. Aim of this study is to assess the medium-term outcome of recipients of marginal donor hearts selected with new echocardiographic techniques over standard criteria. METHODS AND RESULTS: We enrolled 43 recipients of marginal donor hearts: age > 55 years, or < 55 years but with concomitant risk factors, n = 32; acutely improving during stress, n = 3; or slowly improving during hormonal treatment, n = 8. At follow-up (median, 30 months; interquartile range, 21-52 months), 37 of the recipients were still alive. One-year survival was 93%. CONCLUSION: The strict use of new stress-echocardiographic techniques over standard criteria of marginal donor management, together with comprehensive monitoring of the donor, has the potential to substantially increase the number of donor hearts without adverse effects on recipient medium-term outcome.
Assuntos
Ecocardiografia sob Estresse/métodos , Transplante de Coração/mortalidade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Idoso , Angiografia Coronária , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Resultado do TratamentoRESUMO
Two centrifugal pumps, the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA), used in central or peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated, in terms of double-center experience, as treatment for patients with refractory cardiogenic shock (CS). Between January 2006 and December 2012, 228 consecutive adult patients were supported on RotaFlow (n=213) or CentriMag (n=15) ECMO, at our institutions (155 men; age 58.3±10.5 years, range: 19-84 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n=118) and primary donor graft failure (n=37); postacute myocardial infarction CS (n=27); acute myocarditis (n=6); and CS on chronic heart failure (n=40). A peripheral ECMO setting was established in 126 (55.2%) patients while it was established centrally in 102 (44.7%). Overall mean support time was 10.9±9.7 days (range: 1-43 days). Eighty-four (36.8%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n=144), weaning from mechanical support (n=107; 46.9%), bridge to mid-long-term ventricular assist device (n=6; 2.6%), and bridge to heart transplantation (n=31; 13.5%), was 63.1%. One hundred twenty-two (53.5%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and MB isoenzyme of creatine kinase (CK-MB) relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality on ECMO (P=0.010, odds ratio [OR]=2.94; 95% confidence interval [CI]=1.10-3.14; P=0.010, OR=2.82, 95% CI=1.014-3.721; and P=0.011, OR=2.69; 95% CI=1.06-4.16, respectively). Central ECMO population had significantly higher rate of continuous veno-venous hemofiltration need and bleeding requiring surgery events compared with the peripheral ECMO setting population. No significant differences were seen by comparing the RotaFlow and CentriMag populations in terms of device performance. At follow-up, persistent heart failure with left ventricle ejection fraction (LVEF)≤40% was a risk factor after hospital discharge. Patients with a poor hemodynamic status may benefit from rapid central or peripheral insertion of ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support. In addition, early ventricular assist device placement or urgent listing for heart transplant should be considered in patients with persistent impaired LVEF after ECMO.
Assuntos
Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Choque Cardiogênico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Creatina Quinase/sangue , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/instrumentação , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Choque Cardiogênico/sangue , Choque Cardiogênico/cirurgia , Análise de SobrevidaRESUMO
The aim of this study is to investigate the blood perfusion and the inflammatory response of the myocardial infarct area after transplanting a hyaluronan-based scaffold (HYAFF(®) 11) with bone marrow mesenchymal stem cells (MSCs). Nine-week-old female pigs were subjected to a permanent left anterior descending coronary artery ligation for 4 weeks. According to the kind of the graft, the swine subjected to myocardial infarction were divided into the HYAFF(®) 11, MSCs, HYAFF(®) 11/MSCs and untreated groups. The animals were killed 8 weeks after coronary ligation. Scar perfusion, evaluated by Contrast Enhanced Ultrasound echography, was doubled in the HYAFF(®) 11/MSCs group and was comparable with the perfusion of the healthy, non-infarcted hearts. The inflammation score of the MSCs and HYAFF(®) 11/MSCs groups was near null, revealing the role of the grafted MSCs in attenuating the cell infiltration, but not the foreign reaction strictly localized around the fibres of the scaffold. Apart from the inflammatory response, the native tissue positively interacted with the HYAFF(®) 11/MSCs construct modifying the extracellular matrix with a reduced presence of collagene and increased amount of proteoglycans. The border-zone cardiomyocytes also reacted favourably to the graft as a lower degree of cellular damage was found. This study demonstrates that the transplantation in the myocardial infarct area of autologous MSCs supported by a hyaluronan-based scaffold restores blood perfusion and almost completely abolishes the inflammatory process following an infarction. These beneficial effects are superior to those obtained after grafting only the scaffold or MSCs, suggesting that a synergic action was achieved using the cell-integrated polymer construct.
Assuntos
Ácido Hialurônico/química , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Neovascularização Fisiológica , Alicerces Teciduais , Animais , Adesão Celular , Forma Celular , Sobrevivência Celular , Células Cultivadas , Vasos Coronários/fisiopatologia , Matriz Extracelular/metabolismo , Feminino , Células-Tronco Mesenquimais/fisiologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Próteses e Implantes , Sus scrofa , Transplante AutólogoRESUMO
BACKGROUND: Permanence of grafted stem cells in the infarcted myocardial area has been suggested to be favored by tissue engineering strategies, including the application of a scaffold as a cell support. However, an estimation of how many cells remain localized in the site of transplantation has never been done. The aim of this work was to investigate the localization of mesenchymal stem cells (MSCs) grafted with a well cell-adhesive polymer in the scar region of the infarcted heart. MATERIALS AND METHODS: Rat MSCs were engineered in a hyaluronan-based scaffold (HYAFF(®)11) for 3 wk. The hearts of donor rats were also explanted, subjected to coronary artery ligation, and grafted into the abdomen of syngeneic rats. Two wk after coronary ligation a small dish of the HYAFF(®)11/MSC construct was introduced into a pouch created in the ventricular wall of the infarct area and left for 2 wk. RESULTS: Under ex vivo conditions, MSCs tightly adhered to the hyaluronan fibers and secreted abundant extracellular matrix. In contrast, HYAFF(®)11 was not more surrounded by the engrafted MSCs 2 wk after construct transplantation. Most MSCs migrated near the border zone of the infarcted area close to the coronary vessels. Moreover, the infarcted region of the heart was enriched in capillaries and the degree of fibrosis was attenuated. CONCLUSIONS: Two wk after transplantation most MSCs grafted in the infarcted myocardium with HYAFF(®)11 had left the scaffold and moved to the border zone. Nevertheless, this treatment increased the myocardial vascularization and reduced the degree of fibrosis in the scar area.
Assuntos
Ácido Hialurônico , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Cultivadas , Cicatriz/patologia , Vasos Coronários/fisiologia , Modelos Animais de Doenças , Fibrose Endomiocárdica/prevenção & controle , Masculino , Células-Tronco Mesenquimais/patologia , Ratos , Ratos Endogâmicos Lew , Resultado do TratamentoRESUMO
AIMS: Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA). METHODS AND RESULTS: In this Italian multicentre study, 186 patients with ATTR were characterized at presentation. Thirty patients with SSA and 30 age-gender-matched HCM patients were used for comparison. Phenotype was classified as exclusively cardiac (n = 31, 17%), exclusively neurologic (n = 46, 25%), and mixed cardiac/neurologic (n = 109, 58%). Among the eight different mutations responsible for an exclusively cardiac phenotype, Ile68Leu was the most frequent. Five patients with an exclusively cardiac phenotype developed mild abnormalities at neurological examination, but no symptoms during a 36-month follow-up (range: 14-50). Exclusively cardiac phenotype was characterized by male gender, age >65 years, heart failure symptoms, symmetric left ventricular (LV) 'hypertrophy', and moderately depressed LV ejection fraction. This profile was similar to SSA, but relatively distinct from HCM. Compared with patients with a mixed phenotype, patients with an exclusively cardiac phenotype showed a more pronounced cardiac involvement on both echocardiogram and electrocardiogram (ECG). CONCLUSION: A clinically relevant subset of Caucasian ATTR patients present with an exclusively cardiac phenotype, mimicking HCM or SSA. Echocardiographic and ECG findings are useful to differentiate ATTR from HCM but not from SSA. The role of liver transplantation in these patients should be reconsidered.
Assuntos
Neuropatias Amiloides Familiares/genética , Cardiomiopatia Hipertrófica/genética , Mutação/genética , Adulto , Idoso , Neuropatias Amiloides Familiares/diagnóstico , Cardiomiopatia Hipertrófica/diagnóstico , Estudos de Casos e Controles , Diagnóstico Diferencial , Ecocardiografia , Eletrocardiografia , Feminino , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
Splitting the liver for two adults to increase the donor pool is still a debated issue, especially for combined organ transplantation. We described a case of liver-splitting procedure for two adults, which was successful even in the presence of combined organ transplantation. Three adult combined organ transplantations from one deceased donor were performed, with, use of split liver grafts in two patients: a combined heart-right split liver, a left kidney-left split liver, and a right kidney-pancreas transplantation. Despite a not perfect match between the graft type and recipient, the prevention of small-for-size syndrome by ligature of the splenic artery, and/or hemiportocaval shunt in the patient receiving the left split liver, and the maximal reduction of ischemia time were the main factors contributing to the success of the procedure. This is the first report of combined heart and split liver in two adults which may suggest new strategies for organ transplantations.
RESUMO
BACKGROUND: Knowledge of the patterns of myocardial amyloid accumulation could improve the interpretation of electrocardiographic, echocardiographic and magnetic resonance imaging findings of amyloidosis. We assessed the extent and pattern of myocardial amyloid infiltration in explanted or autopsied hearts of patients with cardiomyopathy related to acquired monoclonal immunoglobulin light-chain (AL) or hereditary transthyretin (TTR) related amyloidosis (ATTR). METHODS: We analyzed nine explanted/autopsied hearts from patients with AL (n = 4) and ATTR (n = 5) cardiac amyloidosis. For each heart, a biventricular histological macrosection was obtained at mid-ventricular level and analyzed with both inspective and computer-assisted histologic and histomorphometric analysis aimed in particular at quantifying muscle cells, fibrosis and amyloid infiltration. RESULTS: The extent of amyloid infiltration of the left ventricle (LV) ranged from 45 to 76% (median [interquartile range (IQR)] = 57% [51-64]) of the overall surface. Although LV trabecular and subendocardial were the most infiltrated layers (45-94%, median [IQR] = 73% [67-84] and from 44 to 71%, median [IQR] = 57% [49-59], respectively), intra- and inter-patient heterogeneity was high. Three main patterns of amyloid infiltration of the LV were identified: diffuse (five cases), mainly subendocardial (two cases), and mainly segmental (two cases). The extent of amyloid infiltration of the right ventricle ranged from 48 to 93% (median [IQR] = 61% [59-83]); contributions of parietal and trabecular layers ranged from 32 to 99% (median [IQR] = 63% [47-88]) and from 49 to 93% (median [IQR] = 74% [64-79]), respectively. CONCLUSIONS: In amyloidotic cardiomyopathy, amyloid deposition is highly heterogeneous. Different patterns of infiltration are identifiable, including diffuse, mainly segmental and mainly subendocardial. Awareness of this variability can help the interpretation of ECGs, echocardiograms and magnetic resonance imaging.
Assuntos
Amiloidose Familiar/diagnóstico , Cardiomiopatias/diagnóstico , Amiloidose Familiar/patologia , Amiloidose Familiar/cirurgia , Cardiomiopatias/patologia , Cardiomiopatias/cirurgia , Feminino , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Tamanho do Órgão , Placa Amiloide/metabolismoRESUMO
BACKGROUND: The heart transplant is a treatment of the heart failure, which is not responding to medications. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease, in order to exclude donors with a history of cardiac disease. A simple way to evaluate this should be stress echocardiography. CASE REPORT: A marginal donor (a 57 year old woman meeting legal requirements for brain death) underwent a transesophageal (TE) dipyridamole stress echo (6 minutes accelerated protocol) to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress, without signs of stress inducible ischemia, and there was no latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient marginal for co-morbidity (a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV). The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT) echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant. CONCLUSION: For the first time stress echo was successfully used for the selection of hearts "too good to die", representing a critical way to solve the mismatch between donor need and supply.
Assuntos
Amiloidose/cirurgia , Ecocardiografia sob Estresse , Ecocardiografia Transesofagiana , Cardiopatias/cirurgia , Transplante de Coração , Doadores de Tecidos , Amiloidose/complicações , Morte Encefálica , Dipiridamol , Ecocardiografia sob Estresse/métodos , Ecocardiografia Transesofagiana/métodos , Feminino , Cardiopatias/complicações , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Resultado do Tratamento , VasodilatadoresRESUMO
BACKGROUND: Because of the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Abnormal results on pharmacologic stress echocardiography are associated with significant coronary artery disease and/or occult cardiomyopathy on verification by cardiac autopsy. The aim of this study was to establish the feasibility of an approach based on pharmacologic stress echocardiography as a gatekeeper for extended heart donor criteria. METHODS: From April 2005 to April 2010, 39 "marginal" candidate donors (mean age, 56 ± 6 years; 21 men) were initially enrolled. After legal declaration of brain death, marginal donors underwent rest echocardiography, and if the results were normal, dipyridamole (0.84 mg/kg over 6 min, n = 25) or dobutamine (up to 40 µg/kg/min, n = 3) stress echocardiography. RESULTS: A total of 19 eligible hearts were found with normal findings. Of these, three were not transplanted because of the lack of a matching recipient, and verification by cardiac autopsy showed absence of significant coronary artery disease or cardiomyopathy abnormalities. The remaining 16 eligible hearts were uneventfully transplanted in marginal emergency recipients. All showed normal (n = 14) or nearly normal (minor single-vessel disease in two) angiographic, intravascular ultrasound, hemodynamic and ventriculographic findings at 1 month. At follow-up (median, 14 months; interquartile range, 4-31 months), 14 patients survived and two had died, one at 2 months from general sepsis and one at 32 months from allograft vasculopathy in recurrent multiple myeloma. CONCLUSIONS: Pharmacologic stress echocardiography can safely be performed in candidate heart donors with brain death and shows potential for extending donor criteria in heart transplantation.
Assuntos
Ecocardiografia sob Estresse/métodos , Transplante de Coração , Doadores de Tecidos , Análise de Variância , Morte Encefálica , Cardiotônicos , Distribuição de Qui-Quadrado , Dipiridamol , Dobutamina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Seleção de Pacientes , Análise de Sobrevida , Resultado do Tratamento , VasodilatadoresRESUMO
When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction), arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions), and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo. Aims of this paper are: 1) to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2) to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3) to show examples of software testing in a way that proves its value.The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it.
Assuntos
Instrução por Computador/métodos , Circulação Coronária/fisiologia , Ecocardiografia Tridimensional/métodos , Internet , Modelos Cardiovasculares , Software , Interface Usuário-Computador , Simulação por Computador , Teste de Esforço , Humanos , Itália , Laboratórios HospitalaresRESUMO
BACKGROUND: To resolve the current shortage of donor hearts, we established the Adonhers protocol. An upward shift of the donor age cut-off limit (from the present 55 to 65 years) is acceptable if a stress echo screening on the candidate donor heart is normal. This study aimed to verify feasibility of a "second opinion" of digitally transferred images of stress echo results to minimize technical variability in selection of aged donor hearts for heart transplant. METHODS: The informatics infrastructure was created for a core lab reading with a second opinion from the Pisa stress echo lab. To test the system, simulation standard stress echo cineloops were sent digitally from 5 peripheral labs to the central core lab.Starting January 2009, real marginal donor stress echos were sent via internet to the central core echo lab, Pisa, for a second opinion before heart transplant. RESULTS: In the simulation protocol, 30 dipyridamole stress echocardiograms were sent from the five peripheral echo labs to the central core lab in Pisa. Both the echo images and reports were correctly uploaded in the web system and sent to the core echo lab; the second opinion evaluation was obtained in all cases (100% feasibility). In the transplant protocol, eight donor cases were sent to the Pisa core lab for the second opinion protocol, and six of them were transplanted in marginal recipients. CONCLUSIONS: Second-Opinion Stress Tele-Echocardiography can effectively be performed in a network aimed to safely expand the heart donor pool for heart transplant.
Assuntos
Ecocardiografia sob Estresse , Transplante de Coração , Encaminhamento e Consulta , Telemedicina , Doadores de Tecidos , Idoso , Dipiridamol , Humanos , Pessoa de Meia-Idade , VasodilatadoresRESUMO
BACKGROUND: Owing to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Pharmacologic stress echocardiography is highly accurate in identifying prognostically significant coronary artery disease, but brain death and catecholamine storm in potential heart donors may substantially alter the cardiovascular response to stress. This study assessed correlates of an abnormal resting/stress echocardiography results in potential donors. METHODS: From April 2005 to December 2007, 18 marginal candidate donors (9 men) aged 58 +/- 5 years were initially enrolled. After legal declaration of brain death, all marginal donors underwent bedside echocardiography, with baseline and (when resting echocardiography was normal) dipyridamole (0.84 mg/kg in 6 min) or dobutamine (up to 40 microg/kg/min) stress echo. Non-eligible hearts (with abnormal rest or stress echo findings) were excluded and underwent cardioautoptic verification. RESULTS: Resting echocardiography showed wall motion abnormalities in 5 patients (excluded from donation). Stress echocardiography was performed in the remaining 13 (dipyridamole in 11; dobutamine in 2). Results were normal in 7, of which 6 were uneventfully transplanted in marginal recipients. Results were abnormal in 6, and autoptic verification performed showed coronary artery disease in 5, and initial cardiomyopathy in 1. CONCLUSIONS: Bedside pharmacologic stress echocardiography can safely be performed in candidate heart donors, is able to unmask occult coronary artery disease or cardiomyopathy, and shows potential to extend donor criteria in heart transplantation. Further experience with using marginal donors is needed before exact guidelines can be established.
Assuntos
Ecocardiografia sob Estresse/métodos , Miocárdio/patologia , Doadores de Tecidos/estatística & dados numéricos , Idoso , Morte Encefálica , Dipiridamol/uso terapêutico , Dobutamina , Feminino , Coração/anatomia & histologia , Valvas Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Seleção de Pacientes , PressãoRESUMO
BACKGROUND: New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates. AIM: To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system. METHODS: We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 +/- 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording. RESULTS: Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p < 0.05). At 100 bpm stress heart rate, systolic/diastolic time ratio (normal, < 1) was > 1 in 20 patients and in none of the controls (p < 0.01); at recovery systolic/diastolic ratio was > 1 in only 3 patients (p < 0.01 vs stress). Post-exercise reduced arterial pressure was sensed. CONCLUSION: Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes--in our study, all of these were monitored by a non-invasive wearable sensor.
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Determinação da Pressão Arterial/métodos , Pressão Sanguínea , Diagnóstico por Computador/métodos , Auscultação Cardíaca/métodos , Contração Miocárdica , Telemedicina/métodos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Aceleração , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse MecânicoRESUMO
The PTHrP/PTH1R signalling system induces calciotropic and myorelaxant effects on the vascular system and plays critical roles in the development of the cardiovascular system. In animal models, PTHrP exerts important effects on heart rate and contractility, particularly under ischemic conditions, while, in human hearts, the expression of PTHrP by cardiomyocytes remains to be defined in both normal and ischemic conditions. The present study has been conducted on 101 autoptical cases and confirmed on nine explanted hearts in order to analyze the expression of the PTHrP/PTH1R system by ventricular myocardium in respect to morphological aspects of the myocardial ischemic damage, myofiber hypertrophy and disarray, coronarosclerosis, age and sex. Immunohistochemistry showed positive cytoplasmic immunostaining for both PTHrP and PTH1R in ventricular cardiomyocytes. The expression levels of the PTHrP/PTH1R system resulted significantly increased (P = 0.0008 and P < 0.0001, respectively) in association with the myocardial ischemic damage and the presence of cardiomyocyte hypertrophy (P = 0.02 and P = 0.009 respectively). Conversely, increased expression levels of PTHrP alone were observed in myofiber disarray (P = 0.04), whereas PTH1R was augmented in coronarosclerosis (P = 0.004) and age (P = 0.001). Taken together, these results demonstrate that human ventricular cardiomyocytes express PTHrP and PTH1R and suggest that the activation of the PTHrP/PTH1R system could represent an aspect of the embryonic gene program typically reactivated by the myocardium when subjected to ischemia and/or hypertrophy.
Assuntos
Ventrículos do Coração/metabolismo , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Imunofluorescência , Ventrículos do Coração/patologia , Humanos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Adulto JovemRESUMO
BACKGROUND: Recently, a cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been validated. A further application is the assessment of Second Heart Sound (S2) amplitude variations at increasing heart rates. The aim of this study was to assess the relationship between second heart sound amplitude variations at increasing heart rates and hemodynamic changes. METHODS: The transcutaneous force sensor was positioned in the precordial region in 146 consecutive patients referred for exercise (n = 99), dipyridamole (n = 41), or pacing stress (n = 6). The curve of S2 peak amplitude variation as a function of heart rate was computed as the increment with respect to the resting value. RESULTS: A consistent S2 signal was obtained in all patients. Baseline S2 was 7.2 +/- 3.3 mg, increasing to 12.7 +/- 7.7 mg at peak stress. S2 percentage increase was + 133 +/- 104% in the 99 exercise, + 2 +/- 22% in the 41 dipyridamole, and + 31 +/- 27% in the 6 pacing patients (p < 0.05). Significant determinants of S2 amplitude were blood pressure, heart rate, and cardiac index with best correlation (R = .57) for mean pressure. CONCLUSION: S2 recording quantitatively documents systemic pressure changes.
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Monitores de Pressão Arterial , Pressão Sanguínea , Ecocardiografia sob Estresse , Ruídos Cardíacos , Idoso , Ciclismo , Estimulação Cardíaca Artificial , Dipiridamol , Eletrocardiografia , Feminino , Coração/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Decúbito Dorsal , Resistência VascularRESUMO
BACKGROUND: The current surgical technique for pulmonary endarterectomy (PEA) involves the use of deep hypothermia and circulatory arrest at 18 degrees C (DHCA). Our experience started in 2004 when we decided to use an original alternative strategy which consists of avoiding deep hypothermia and subsequent circulatory arrest by using moderate hypothermia at 26 degrees C, and maintaining a bloodless field. This can be achieved by means of negative pressure in the left heart chambers and appropriate pump flow modulation in order to maintain the mixed venous oxygen saturation (SVO(2)) higher than 65%. MATERIALS AND METHODS: From June 2004 to June 2007, 40 consecutive patients were operated on in our department with this strategy. The aim of this article is to report the early results for all patients and the complete six-month follow-up for 30 subjects who have reached this end-point at the time of writing. The mean temperature during extracorporeal circulation was 25.9 degrees C; core temperature was lowered to 21 degrees C in only one patient and an 8 min DHCA was performed in order to complete the PEA. RESULTS: Two patients died (6.6%): one on the third postoperative day due to myocardial infarct, requiring an ECMO implantation. The other patient died from septic shock. The six-month follow-up, performed in all other patients, included clinical and hemodynamic evaluation. Pulmonary vascular resistance (PVR) decreased from 793.5+/-284 dyn/cm/s(-5) to 286+/-143 (p=0.000). A comparable reduction of mean pulmonary arterial pressure and an increase of cardiac output were also observed. CONCLUSIONS: The results confirm that adequate removal of pulmonary artery obstructive lesions can also be achieved with an operative procedure that avoids or reduces the use of DHCA while allowing a bloodless field during PEA interventions. This technique may limit the well known adverse effects of DHCA due to organ hypoperfusion, improving the postoperative recovery of the patients.
Assuntos
Parada Circulatória Induzida por Hipotermia Profunda , Endarterectomia/métodos , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/cirurgia , Resistência VascularRESUMO
UNLABELLED: A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration. AIMS: 1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress. METHODS: We enrolled 161 patients referred for stress echocardiography (exercise 115, dipyridamole 40, pacing 6 patients).The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal. Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time. RESULTS: Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 +/- 0.12) than in patients (0.86 +/- 0.10, p < 0.05 vs. controls). Diastolic filling rate increased from 101 +/- 36 (rest) to 219 +/- 92 ml/m2* s-1 at peak stress (p < 0.5 vs. rest). CONCLUSION: Cardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate.Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress.
Assuntos
Circulação Coronária , Diástole , Auscultação Cardíaca/métodos , Modelos Cardiovasculares , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia , Simulação por Computador , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como AssuntoRESUMO
BACKGROUND: More evidence is needed to assess the pros and cons of maintaining age-limit policies in heart transplantation (HT). METHODS: We analyzed clinical data from a heart failure management unit to investigate the impact of age on prognosis of two distinct cohorts: (i) 309 patients (median age, 57 yr; 62% male) with severe chronic heart failure (CHF) consecutively screened for HT; (ii) 336 HT recipients (median age 56 yr, 82% male). RESULTS: In CHF patients (screened for HT), prognosis was conditioned by the underlying severity of cardiac disease (i.e., New York Heart Association class III-IV, decreasing blood pressure, presence of atrial fibrillation and severe mitral regurgitation), whereas increasing age showed no sign of predicting all-cause or cardiovascular mortality (both p > or = 0.4). In HT recipients, age did not retain significance at multivariate analysis as an independent predictor (p > or = 0.14 for both all-cause and cardiovascular death), whereas ischemic etiology of pre-existing CHF did (p < or = 0.02). CONCLUSIONS: Age did not appear to be a primary determinant of all-cause or cardiovascular mortality among potential HT candidates or eventual recipients (ischemic etiology of CHF turned out to be the major determinant of post-transplant outcome). These results support the concept that HT may be considered a treatment option in patients with more advanced age strata, particularly when affected by non-ischemic cardiomyopathy.
Assuntos
Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Insuficiência Cardíaca/complicações , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Prognóstico , Estudos RetrospectivosRESUMO
Ischemic cardiomyopathy is the most common cause of dilated cardiomyopathy and congestive heart failure. It affects approximately 1 out of 100 people, most often middle-aged to elderly men. Left ventricular restoration surgery is a challenging therapeutic approach to this pathology: it aims to rebuild a near-normal ventricular chamber in a heart damaged by a myocardial infarction, reducing its volume and improving the fraction of blood ejected by each systole. This is obtained by eliminating the akinetic/dyskinetic part of the cardiac muscle and closing the final defect with or without a synthetic patch. Optimization of surgical repair is mandatory as far as ischemic cardiomyopathy is a worldwide disease responsible for many cardiac deaths and because of its potential use as an alternative to heart transplantation in selected patients. Until now, this surgery has been performed without caring for myocardial fibers' disposition but recent evidences clarified the key role of fibers' alignment in heart physiology. The myocardium of the left ventricle has a unique three-dimensional, multilayered structure: it constitutes the anatomical basis for the cardiac function and for left ventricular torsion, a key movement of normal heart. Myocardial infarction alters myocardial structure in the site of the necrosis and subsequent cardiomyopathy eliminates left ventricular torsion. On the other hand, histological evidences show that myofibers' orientation in the thickness of residual normal myocardium is not changed and that transmural courses of fiber orientation angles near infarct zones were similar to those of normal myocardium. We hypothesize that, with a particular surgical technique, it could be possible to realign the anatomically normal fibers of the residual myocardium in order to rebuild a physiologic setting. We planned a novel surgical technique of left ventricular restoration using a very narrow, string-shaped patch and a particular suturing sequence and technique, whose aim is to near normally oriented residual myocardial fibers. The renewal of left ventricular torsion was evident at sight just at the end of this kind of ventricular restoration, still in the operating room, then confirmed by 2D speckle tracking echocardiography. These observations are indirect proofs of fibers' realignment, as the torsion movement of the left ventricle is due to the interlaced, oblique orientation of myocardial fibers. We herein propose a theoretical explanation of this outcome, drawing a geometrical modeling of the surgical procedure.
Assuntos
Cardiomiopatias/cirurgia , Cardiomiopatias/terapia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Procedimentos Cirúrgicos Operatórios , Cirurgia Torácica/métodos , Cardiologia/métodos , Ecocardiografia/métodos , Ventrículos do Coração/patologia , Humanos , Modelos Anatômicos , Modelos Biológicos , Modelos Teóricos , Miocárdio/metabolismo , Remodelação VentricularRESUMO
beta-Thalassaemia is an inherited haemoglobin (Hb) disorder resulting in chronic haemolytic anaemia. The most anaemic patients require regular red blood cell (RBC) transfusions for survival but iron accumulation leads to multisystem dysfunction. Heart complications represent the leading cause of mortality in beta-thalassaemia patients. In this case report we present a successful mitral valve replacement (MVR) in a patient with a severe form of beta-thalassaemia.