RESUMO
BACKGROUND: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. CONCLUSIONS: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.
Assuntos
Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/terapia , Internacionalidade , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/terapia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. RESULTS: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. TRIAL REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Tromboembolia/complicações , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Doença Crônica , Esquema de Medicação , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Síncope/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. METHODS AND RESULTS: The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments.
Assuntos
Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/cirurgia , Sistema de Registros , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/cirurgia , Idoso , Doença Crônica , Endarterectomia/mortalidade , Antagonistas dos Receptores de Endotelina , Feminino , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Incidência , Internacionalidade , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Prospectivos , Prostaglandinas I/uso terapêutico , Recidiva , Fatores de Risco , Filtros de Veia Cava/estatística & dados numéricos , Tromboembolia Venosa/tratamento farmacológicoRESUMO
A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial Hypertension) was undertaken to analyse prevalence, incidence and survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Spain, and to assess the applicability of recent survival prediction equations. Voluntary reporting of previously diagnosed and incident PAH or CTEPH cases (July 2007-June 2008) was performed. Demographic, functional and haemodynamic variables were evaluated. 866 patients with PAH and 162 with CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno-occlusive disease were reported for the first time in a PAH registry. Estimated prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9 cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%, respectively, with no differences between PAH and CTEPH. Male sex, right atrial pressure and cardiac index were independent predictors of death. Matching between observed survival and that predicted by different equations was closer when the characteristics of the cohorts were similar. Epidemiology and survival of PAH patients in the Spanish registry are similar to recent registries. Characteristics of the population from which survival prediction equations are derived influence their applicability to a different cohort. CTEPH is much less prevalent than PAH, although has a similar survival rate.
Assuntos
Hipertensão Pulmonar/mortalidade , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Prevalência , Pneumopatia Veno-Oclusiva/epidemiologia , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Espanha/epidemiologia , Tromboembolia/epidemiologiaRESUMO
The longer survival of patients with heart transplantation (HT) favors calcineurin inhibitor-related chronic kidney disease (CKD). It behoves to identify risk factors. At 14 Spanish centers, data on 1062 adult patients with HT (age 59.2 ± 12.3 yr, 82.5% men) were collected at routine follow-up examinations. Glomerular filtration rate, GFR, was estimated using the four-variable MDRD equation, and moderate-or-severe renal dysfunction (MSRD) was defined as K/DOQI stage 3 CKD or worse. Time since transplant ranged from one month to 22 yr (mean 6.7 yr). At assessment, 26.6% of patients were diabetic and 63.9% hypertensive; 53.9% were taking cyclosporine and 33.1% tacrolimus; and 61.4% had MSRD. Among patients on cyclosporine or tacrolimus at assessment, multivariate logistic regression identified male sex (OR 0.44), pre- and post-HT creatinine (2.73 and 3.13 per mg/dL), age at transplant (1.06 per yr), time since transplant (1.05 per yr), and tacrolimus (0.65) as independent positive or negative predictors of MSRD. It is concluded that female sex, pre- and one-month post-HT serum creatinine, age at transplant, time since transplant, and immunosuppression with cyclosporine rather than tacrolimus may all be risk factors for development of CKD ≥ stage 3 by patients with HT.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Nefropatias/etiologia , Adolescente , Adulto , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2. METHODS: RRS was calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT-2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were made for survival and clinical worsening-free survival in PATENT-2 to evaluate the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2. RESULTS: A total of 396 patients completed PATENT-1 and participated in PATENT-2. In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675, 0.705 and 0.804, respectively) and clinical worsening-free survival (hazard ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2. CONCLUSIONS: RRS at baseline and Week 12, and change in RRS, were significant predictors of both survival and clinical worsening-free survival. These data support the long-term predictive value of the RRS in a controlled study population.
Assuntos
Ativadores de Enzimas/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/mortalidade , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Idoso , Algoritmos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Mutations of the BMPR2 gene predispose to pulmonary arterial hypertension (PAH), a serious, progressive disease of the pulmonary vascular system. However, despite the fact that most PAH families are consistent with linkage to the BMPR2 locus, sequencing only identifies mutations in some 55% of familial cases and between 10% and 40% of cases without a family history (idiopathic or IPAH). We therefore conducted a systematic analysis for larger gene rearrangements in panels of both familial and idiopathic PAH cases that were negative on sequencing of coding regions. Analysis of exon dosage across the entire gene using Multiplex Ligation-dependent Probe Amplification identified nine novel rearrangements and enabled full characterization at the exon level of previously reported deletions. Overall, BMPR2 rearrangements were identified in 7 of 58 families and 6 of 126 IPAH cases, suggesting that gross rearrangements underlie around 12% of all FPAH cases and 5% of IPAH. Importantly, two deletions encompassed all functional protein domains and are predicted to result in null mutations, providing the strongest support yet that the predominant molecular mechanism for disease predisposition is haploinsufficiency. Dosage analysis should now be considered an integral of part of the molecular work-up of PAH patients.
Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Rearranjo Gênico , Predisposição Genética para Doença , Hipertensão Pulmonar/genética , Mutação , Artéria Pulmonar/patologia , Análise Mutacional de DNA , Feminino , Deleção de Genes , Dosagem de Genes , Ligação Genética , Humanos , Masculino , Modelos GenéticosRESUMO
BACKGROUND: Antilymphocytic antibodies have been long used for the prevention of acute rejection early after heart transplantation (HTx), but their adverse effects have limited their widespread use. Our aim was to evaluate the safety, tolerability, and efficacy of the novel anti-CD25 antibody basiliximab (BAS) compared with muromonab (OKT3). PATIENTS AND METHODS: In this multicenter study, 99 patients were randomly assigned to receive either BAS or OKT3 in the early post-HTx period. The primary endpoint was safety and tolerability. Specific safety variables were predefined for a better comparison of adverse effects. Secondary endpoints concerning anti-rejection efficacy were also evaluated. RESULTS: No adverse events related to study medication were found in the BAS group, whereas 23 were observed among patients receiving OKT3 (P<0.0001). The proportion of patients with predefined adverse events day 4 post-HTx was much higher with OKT3 than with BAS (43% vs. 4%; P<0.0001). Fever, acute pulmonary edema, hypotension, and other complications accounted for most of the difference. At 1-year follow-up, biopsy-proven rejection episodes grade>or=3A had occurred in 39.6% of BAS patients versus 40.4% of OKT3 patients (P=0.87). There were no differences in terms of severity and timing of acute rejection episodes. The number of infectious episodes, complications not related to study medication, and actuarial survival were similar in both groups. CONCLUSION: In this HTx study, induction therapy with BAS was safer and better tolerated than OKT3, without significant differences in efficacy outcomes.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Imunossupressores/uso terapêutico , Muromonab-CD3/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Basiliximab , Tolerância a Medicamentos/imunologia , Feminino , Febre/induzido quimicamente , Febre/diagnóstico , Humanos , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/efeitos adversos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/diagnóstico , Proteínas Recombinantes de Fusão/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Prostacyclin improves symptoms, exercise tolerance, and survival in patients with pulmonary arterial hypertension. However, the difficulty of administration (whether intravenous, subcutaneous, or by inhalation) often causes side effects that can reduce the patient's quality of life and which may sometimes be serious. Bosentan, an orally active endothelin receptor antagonist, improves functional class and exercise tolerance in these patients. We describe the successful transition from prostacyclin to bosentan in five patients with severe pulmonary arterial hypertension who suffered serious side effects with prostacyclin treatment.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Bosentana , Epoprostenol/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Pulmonary hypertension (PH) is a disease of various origins. Nitric oxide-a potent vasodilator-is a key player of pulmonary vasoregulation. Nitric oxide signaling is mainly mediated by the guanylate cyclase/cyclic guanylate monophosphate pathway. The effects of this second messenger system are limited by enzymatic degradation through phosphodiesterases (PDEs). Recently, beneficial effects of the oral PDE-5 inhibitor sildenafil (originally approved for the treatment of erectile dysfunction) were reported for the treatment of PH. We provide a brief overview of the experimental and clinical application of PDE inhibitors in the field of PH. In particular, studies reporting the clinical effectiveness of sildenafil are highlighted. This agent, despite oral application, displays characteristics of a pulmonary selective vasodilator. In addition, evidence shows that sildenafil is operative mainly in the vasculature of well-ventilated areas of the lung. However, to date, controlled randomized trials proving the efficacy of this approach for the treatment of pulmonary arterial hypertension are lacking. The results of such studies have to confirm the current encouraging findings before recommendations regarding the use of PDE-5 inhibitors as a new treatment for PH can be made.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Óxido Nítrico/metabolismo , Inibidores de Fosfodiesterase/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Piperazinas/uso terapêutico , Purinas , Citrato de Sildenafila , Sulfonas , Vasodilatadores/uso terapêuticoRESUMO
UNLABELLED: Pulmonary hypertension (PHT) associated with chronic heart failure (CHF) is a risk factor of right ventricular failure after heart transplantation (HT). Our aim was to study pulmonary vascular changes in patients with CHF and to assess any correlation with haemodynamic data. METHODS: We studied 17 HT recipients with preoperative CHF who died shortly after HT. Preoperative haemodynamic information was obtained immediately before HT. Vascular lesions in muscular arteries were assessed by linear morphometry. Haemodynamic data were correlated with the morphologic changes. RESULTS: Mean transpulmonary gradient (TPG) was 8.9+/-4.5 mm Hg and pulmonary vascular resistance (PVR) was 2.25+/-1.34 Wu. According to the threshold for at-risk PHT (TPG>12 mm Hg or PVR>2.5 Wu), six patients had at-risk PHT. Medial thickness was 23.82+/-7.23% in patients with at-risk PHT and 17.16+/-3.24% in patients without at-risk PHT (p=0.018). CONCLUSIONS: Medial hypertrophy of muscular pulmonary arteries is more common and severe than expected in patients with CHF, even in patients without at-risk PHT. This structural change could explain why PHT, even in range of values not excluding HT, is a risk factor for right ventricular failure after HT and influences post-HT haemodynamic behaviour.
Assuntos
Causas de Morte , Insuficiência Cardíaca/patologia , Transplante de Coração/mortalidade , Hipertensão Pulmonar/patologia , Artéria Pulmonar/patologia , Disfunção Ventricular Esquerda/mortalidade , Adulto , Doença Crônica , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Transplante de Coração/métodos , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios , Probabilidade , Artéria Pulmonar/fisiopatologia , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Disfunção Ventricular Esquerda/diagnósticoRESUMO
Treatment of arterial pulmonary hypertension with epoprostenol (intravenous prostacyclin) improves survival and quality of life, but the need for an implanted central venous catheter is associated with frequent complications, that often (as in the case of infection or dislodgment) are serious and require catheter replacement. Treprostinil is a prostacyclin analogue suitable for continuous subcutaneous administration. We report the successful transition from intravenous epoprostenol to subcutaneuos treprostinil in four patients with severe pulmonary hypertension who suffered from serious complications associated with the epoprostenol infusion system.
Assuntos
Anti-Hipertensivos/administração & dosagem , Epoprostenol/análogos & derivados , Epoprostenol/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Adulto , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Feminino , Humanos , Infusões Intravenosas/efeitos adversos , Injeções Subcutâneas , Pessoa de Meia-IdadeRESUMO
INTRODUCTION AND OBJECTIVE: Prostacyclin therapy is an effective treatment for severe pulmonary hypertension. Sildenafil, a selective phosphodiesterase type 5 inhibitor, induces selective vasodilatation of the pulmonary vessels. A synergistic effect has been described for these two drugs. The aim of this study was to evaluate the efficacy and safety of sildenafil as rescue therapy in patients with severe pulmonary hypertension on chronic treatment with prostacyclin whose clinical or functional course was unsatisfactory. PATIENTS AND METHOD: Observational study of 11 patients (7 men, 4 women, mean age 42 [8] years) diagnosed as having severe idiopathic pulmonary hypertension, who were receiving chronic prostacyclin therapy. Sildenafil was started after a worsening of their clinical or functional status. Baseline, 3-month and 12-month follow-up evaluations were based on functional status (NYHA functional class and 6-minute walking test), the presence of decompensated right heart failure and echocardiogram. RESULTS: Seven of the 11 patients showed significant improvements in exercise capacity (distance walked in 6 minutes) at 3 (+25 m) and 12 months' follow-up (+36 m). Improvements in functional class were seen, and heart failure disappeared. No significant adverse effects of sildenafil were detected. The echocardiographic parameters showed a significant reduction in right ventricular end-diastolic diameter and left ventricular diastolic eccentricity index. One patient died after 4 months of follow-up from sudden cardiac death. CONCLUSIONS: The addition of oral sildenafil to chronic prostacyclin treatment in patients with severe pulmonary hypertension improved functional capacity and reduced episodes of decompensated right heart failure, with good tolerance and no significant adverse effects.
Assuntos
Anti-Hipertensivos/administração & dosagem , Epoprostenol/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Inibidores de Fosfodiesterase/administração & dosagem , Piperazinas/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Oral , Adulto , Interpretação Estatística de Dados , Quimioterapia Combinada , Ecocardiografia , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Purinas , Segurança , Citrato de Sildenafila , Sulfonas , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVE: The treatment of pulmonary hypertension associated with infection by human immunodeficiency virus has not been well defined. Treprostinil is a prostacyclin analogue that has recently been shown to be useful for the treatment of pulmonary hypertension, whether primary, secondary to congenital heart disease, or associated with collagen disease, in a 12-week, double-blind study. We report the results of a one-year follow-up of three patients with pulmonary hypertension associated with human immunodeficiency virus infection who are being treated with treprostinil at our center. PATIENTS AND METHOD: After secondary causes of pulmonary hypertension were excluded by a routine work-up, patients started treatment with subcutaneous prostacyclin (treprostinil) with progressive up-titration of the dose. Functional status and effort capacity were assessed every three months and an echocardiographic study was performed every six months. RESULTS: All patients showed improvement in clinical status, as shown by the NYHA functional class and the results of the six-minute walking test (increase of at least 75 meters). All the patients remain alive after one year of follow-up. Echocardiographic systolic pulmonary pressure decreased in two patients. No serious adverse events were observed. CONCLUSIONS: Subcutaneous prostacyclin (treprostinil) seems to be an effective and safe therapeutic option for the treatment of pulmonary hypertension associated with human immunodeficiency virus infection.
Assuntos
Anti-Hipertensivos/uso terapêutico , Epoprostenol/uso terapêutico , Infecções por HIV/complicações , Hipertensão Pulmonar/tratamento farmacológico , Adulto , Epoprostenol/análogos & derivados , Feminino , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/etiologia , Bombas de Infusão , Infusões Intravenosas , Masculino , Resultado do Tratamento , Vasodilatadores/uso terapêuticoRESUMO
Individualization of induction therapy for heart transplantation (HT) is needed, given that only patients at significant risk for fatal rejection seem to present a favorable risk-benefit ratio. The question whether monoclonal interleukin 2 antagonists or antilymphocyte antibodies should be recommended remains unanswered. As most studies suggest that they have similar efficacy in preventing acute rejection, other variables related to safety or management costs should be taken into account. The cytokine release syndrome, associated with the use of OKT3, complicates management of HT patient. The experience in our center with 2 consecutive cohorts, treated with basiliximab (BAS) and OKT3, respectively, suggests that the use of BAS is associated, in addition to similar immunosuppressive efficacy and better safety profile than OKT3, with simpler patient management during the initial hospital stay, which could be associated with a reduction in posttransplant costs. Because few centers continue to use OKT3 as induction therapy in HT, more studies comparing cost-effectiveness of BAS vs polyclonal antilymphocyte antibodies (ATG) are needed.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Imunossupressores/administração & dosagem , Muromonab-CD3/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Basiliximab , Rejeição de Enxerto/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
This article contains a review of the main developments in the field of geriatric cardiology reported during 2007, and discusses recent consensus statements. The article focuses on work dealing with the specific characteristics of elderly patients with ischemic heart disease, arrhythmias, heart failure, pulmonary hypertension and valvular heart disease.
Assuntos
Cardiopatias , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Cardiologia , Geriatria , Cardiopatias/diagnóstico , Cardiopatias/terapia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/terapia , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/terapiaRESUMO
The continued aging of the population is an acknowledged fact. The proportion of individuals in the European Union aged over 65 years will reach 29.9% by 2050, almost double the present figure of 16.4%. Approximately one third of people in this age-group has clinically significant cardiovascular disease. Physicians dealing with cardiology in older patients have to be aware of the specific clinical and prognostic features of cardiovascular disease in the elderly, and with its treatment. Consequently, it is clear that continuing medical education in geriatric cardiology is essential, and that is one of the tasks of the Working Group on Geriatric Cardiology. This special issue provides a magnificent opportunity for presenting an update on important topics in geriatric cardiology, such as the aging of the cardiovascular system, heart failure, and atrial fibrillation.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Fatores Etários , Fibrilação Atrial/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , PrognósticoRESUMO
To identify the clinical factors associated with acute rejection (AR) in the first year after heart transplantation (HT), we analysed 112 patients. All patients received OKT3 and standard triple-drug therapy. We analysed the following variables to determine their relationship with AR: age and gender, panel-reactive antibodies, HLA-DR mismatch, use of Sandimmune vs Neoral, diltiazem administration, and cyclosporine levels in week 2 and months 1, 2, and 3 after HT. Fifty-two patients had no AR and 49 had at least one episode. The variables independently associated with absence of AR were diltiazem administration (odds ratio 0.306, confidence limit 0.102-0.921) and cyclosporine level in the first month after HT (odds ratio 0.996, confidence limit 0.992-0.999). Furthermore, a cyclosporine level greater than 362 ng/ml in the first month predicted the absence of AR. In conclusion, a cyclosporine level greater than 362 ng/ml and diltiazem administration in the first month after HT reduce AR during the first year. Both cyclosporine level and diltiazem show a large and independent protective effect.
Assuntos
Anti-Hipertensivos/uso terapêutico , Ciclosporina/sangue , Diltiazem/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Imunossupressores/sangue , Doença Aguda , Adolescente , Adulto , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Fatores de TempoRESUMO
Los pacientes incluidos en lista de espera de trasplante cardiaco frecuentemente presentan un perfil acorde a las recomendaciones actuales en cuanto al implante de desfibrilador automático implantable como prevención primaria de muerte súbita. El eventual trasplante a corto-medio plazo hace dudar de la efectividad de dicha terapia. Analizamos la incidencia de terapias administradas por el desfibrilador implantado como prevención primaria en pacientes en lista, así como la evolución histórica en la frecuencia de muerte súbita en nuestro centro. Se revisaron los 308 pacientes incluidos en lista desde 1998 hasta 2008. En 17 pacientes se indicó desfibrilador automático implantable como prevención primaria al momento de la inclusión. El 53% de éstos recibió terapias adecuadas, habiendo portado el dispositivo una media de 7,8 meses (±4,8). Sólo 1 paciente presentó terapias inadecuadas y ninguno sufrió complicaciones asociadas al dispositivo. La frecuencia de muerte súbita se ha reducido a lo largo de los últimos años(AU)
Patients who are on a waiting list for cardiac transplantation often have a clinical profile that satisfies current recommendations for the implantation of an implantable cardioverterdefibrillator for the primary prevention of sudden death. The prospect that transplantation may take place within the shortto- medium term puts the effectiveness of this therapy in doubt. We investigated the incidence of therapy delivered by implantable cardioverterdefibrillators implanted for primary prevention in patients awaiting cardiac transplantation. Recent changes in the incidence of sudden death at our center were also investigated. Data on 308 patients listed for heart transplantation between 1998 and 2008 were reviewed. An implantable cardioverterdefibrillator was indicated for primary prevention at initial evaluation in 17 patients. Of these, 53% received appropriate implantable cardioverterdefibrillator therapy while carrying an implantable cardioverterdefibrillator for amean period of 7.8months (+/-4.8). Only one patient received inappropriate therapy and none had any complications associated with device use. The frequency of sudden death has decreased over the course of recent years(AU)