RESUMO
PURPOSE: Observational studies indicate a positive association between circulating 25-hydroxyvitamin D (25OHD) and testosterone (T) concentrations. Because low 25OHD concentrations and T deficiency are considered to be a generalized phenomenon in patients with advanced heart failure (HF), we aimed to investigate whether vitamin D supplementation has beneficial effects on T indices in these patients. METHODS: In a pre-specified secondary analysis of the EVITA (effect of vitamin D on mortality in heart failure) randomized controlled trial, we analyzed in male subjects with 25OHD concentrations < 75 nmol/L the effect of a daily vitamin D3 supplement of 4000 IU for 3 years (n = 71) vs. placebo (n = 62) on total T (TT), sex hormone-binding globulin (SHBG), free T (fT), and bioactive T (BAT). We assessed changes from baseline until study termination and between-group differences at study termination. RESULTS: 25OHD increased in the placebo group from 36.6 nmol/L by 9.2 nmol/L (95% CI 3.2-15.1 nmol/L; P = 0.003) and in the vitamin D group from 36.5 nmol/L by 63.9 nmol/L (95% CI 52.6-75.3 nmol/L; P < 0.001), with a significant between-group difference at study termination (P < 0.001). TT and SHBG concentrations did not change significantly, neither in the placebo group nor in the vitamin D group (P = 0.845-0.082), but concentrations of fT and BAT declined significantly in both groups (P = 0.025-0.008). At study termination, there were no between-group differences in TT (P = 0.612), SHBG (P = 0.393), fT (P = 0.861), or BAT (P = 0.960). CONCLUSIONS: In male patients with advanced HF and low 25OHD concentrations, a daily vitamin D3 supplement of 4000 IU for 3 years did not prevent the decline in testosterone indices.
Assuntos
Suplementos Nutricionais , Insuficiência Cardíaca/complicações , Testosterona/sangue , Deficiência de Vitamina D/complicações , Vitamina D/administração & dosagem , Vitamina D/sangue , Seguimentos , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/análogos & derivados , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Vitaminas/sangueRESUMO
BACKGROUND/AIMS: We aimed to investigate the effect of a moderately high vitamin D dose on lipid parameters and biochemical markers of vascular calcification (VC) in patients with established cardiovascular disease. METHODS: We included in this pre-specified secondary analysis of a randomized controlled trial 161 patients with advanced heart failure and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L (vitamin D group: n = 80; placebo group: n = 81), who received a daily vitamin D3 supplement of 4,000 IU for 3 years. We assessed between-group differences of the lipid parameters total-cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides, and the VC markers fetuin-A and non-phosphorylated undercarboxylated matrix gla protein (MGP) at study termination, with adjustment for baseline values. RESULTS: Lipid parameters, the percentage of patients with dyslipoproteinemia, and VC markers did not differ significantly between groups at study termination (p values: 0.395-0.939). Likewise, vitamin D achieved no significant treatment effect on these markers in subgroup analyses in patients with 25OHD concentrations < 30 nmol/L, nonusers of lipid-lowering drugs, or diabetic patients (p values: 0.245-0.998). CONCLUSION: Our data indicate that vitamin D does not improve the lipid profile and does not influence the calcification inhibitors fetuin-A and non-phosphorylated undercarboxylated MGP in patients with advanced heart failure.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Insuficiência Cardíaca/complicações , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Colesterol/sangue , Proteínas da Matriz Extracelular/sangue , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , alfa-2-Glicoproteína-HS/análise , Proteína de Matriz GlaRESUMO
AIMS: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated with a nonlinear increase in mortality risk. Such 25OHD levels are common in heart failure (HF). We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF. METHODS AND RESULTS: Four hundred HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause mortality. Key secondary outcome measures included hospitalization, resuscitation, mechanical circulatory support (MCS) implant, high urgent listing for heart transplantation, heart transplantation, and hypercalcaemia. Initial 25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n = 15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10) and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192). CONCLUSION: A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants. Data indicate caution regarding long-term supplementation with moderately high vitamin D doses. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov Idenitfier: NCT01326650.
Assuntos
Insuficiência Cardíaca/dietoterapia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/mortalidade , Causas de Morte , Suplementos Nutricionais , Feminino , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/dietoterapiaRESUMO
BACKGROUND: Heart transplantation (HTx) is still considered the therapeutic gold standard in end-stage heart failure. METHODS: In "high urgent" (HU)-listed patients for HTx (n = 274) and patients receiving left ventricular assist device (LVAD) implants (n = 332), we compared 1-year overall survival (primary endpoint) and 1-year probability of HTx and therapy failure (the need for LVAD implantation in HU-listed patients or the need for HU listing in LVAD patients) (secondary endpoints). RESULTS: In the HU and LVAD group, 1-year survival was 86.8 and 64.7%, respectively (p < 0.001). The propensity score (PS)-adjusted hazard ratio of mortality did not differ between the groups and for the LVAD group (reference = HU group) was = 1.36 (95% confidence interval [CI]: 0.85-2.19; p = 0.198). The PS-adjusted hazard ratio for the failure to receive HTx for the LVAD group (reference = HU group) was = 9.77 (95% CI: 6.00-15.89; p < 0.001). The corresponding hazard ratio for therapy failure for the LVAD group was = 0.16, 95% CI: 0.10-0.27; p < 0.001). CONCLUSION: Despite considerable differences in the probability of HTx and therapy failure, 1-year overall survival was similar in HU and LVAD patients.
Assuntos
Insuficiência Cardíaca/terapia , Transplante de Coração , Coração Auxiliar , Função Ventricular Esquerda , Listas de Espera , Adulto , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Modelos de Riscos Proporcionais , Desenho de Prótese , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidadeRESUMO
We report the first documented case of a Mycobacterium tuberculosis transmission by an orthotopic heart transplantation from the donor to the recipient. Mycobacterium tuberculosis positive blood culture showed systemic prevalence of the Mycobacteria, however, prophylactic therapy was able to prevent a clinical manifestation of tuberculosis in the recipient.
Assuntos
Antituberculosos/uso terapêutico , Quimioprevenção/métodos , Transplante de Coração/efeitos adversos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/prevenção & controle , Tuberculose/transmissão , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Renal impairment is a risk factor for poor clinical outcome in cardiac surgical patients and low circulating levels of the vitamin D hormone 1,25-dihydroxyvitamin D (1,25[OH](2)D) may contribute to this risk. METHODS: We investigated the association between glomerular filtration rate (GFR) and 1,25(OH)(2)D in 151 heart transplant recipients and 59 other cardiac surgical patients in postoperative week 1 and at postoperative month 1. GFR estimates (eGFR) were calculated from cystatin C (CysC) and serum creatinine (SCr)-based formulas. RESULTS: With both formulas, linear models provided a better fit between eGFR and circulating 1,25(OH)(2)D than nonlinear models. Nonetheless, the association between 1,25(OH)(2)D and eGFR in the early postoperative period was stronger with the CysC-based formula (r = 0.560; P <0.001) than with the SCr-based equation (r = 0.386; P <0.001). CysC-eGFR and SCr-eGFR displayed considerably lack of agreement in the early postoperative period, especially in heart transplant recipients. CONCLUSIONS: There is a relatively close association between CysC-eGFR and circulating 1,25(OH)(2)D in cardiac surgical patients. Data underline the importance of preserved kidney function in cardiac surgery for adequate circulating 1,25(OH)(2)D levels. The SCr-based formula is probably too imprecise for estimating GFR in the early postoperative period correctly.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Taxa de Filtração Glomerular , Nefropatias/etiologia , Rim/fisiopatologia , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Creatinina/sangue , Cistatina C/sangue , Feminino , Transplante de Coração/efeitos adversos , Humanos , Rim/metabolismo , Nefropatias/sangue , Nefropatias/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Dinâmica não Linear , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
BACKGROUND: Circulating graft-derived cell-free DNA (dd-cfDNA) is a new marker of cardiac allograft damage that is used for noninvasive rejection diagnostics. We performed dd-cfDNA (%) in heart transplant recipients during the first posttransplant year. METHODS: In 87 patients, serial dd-cfDNA determination at predefined time-points was performed in 770 single samples. dd-cfDNA fraction (%) was measured using an established universal droplet digital polymerase chain reaction method, providing same-day turn-around. Rejection was diagnosed according to clinical parameters and biopsies. RESULTS: Median dd-cfDNA (%) was high (5.36%) immediately after reperfusion and decreased to a median (interquartile range) of 0.10% (0.05%-0.24%) in clinically stable patients by postoperative day 10. Compared to dd-cfDNA (%) samples in clinically stable patients, values were higher (P < 0.001) in biopsy-proven rejection ISHLT 1R (0.42% [0.15%-0.53%]) and 2R rejection (0.84% [0.39%-0.97%]). Moreover, dd-cfDNA (%) was already significantly increased 9-30 days before biopsy-proven rejection (0.36% [0.20%-0.61%]). An as yet unknown finding was a slightly, but significantly (P < 0.0001) higher dd-cfDNA (%) value in samples of stable patients with pericardial effusions (PEs) (n = 94; 0.18% [0.07%-0.30%]) compared to samples of non-PE patients (n = 132; 0.07% [0.04%-0.17%]). Using a cutoff of 0.35%, sensitivity and specificity of dd-cfDNA for cardiac rejection were 0.76 and 0.83 (area under the curve [AUC] ROC-curve: 0.81 [95% confidence interval, 0.73-0.89]). Omitting PE samples from the control group yielded an AUC of 0.86 [95% confidence interval, 0.76-0.95]. Samples drawn <12 hours after endomyocardial biopsy showed high (0.40% [0.15%-1.21%]) dd-cfDNA values, also in ISHLT0R (0.36% [0.10%-0.60%]). CONCLUSIONS: dd-cfDNA plasma values were significantly associated with cardiac rejection. However, PE or improper sampling (eg, shortly after biopsy) should be considered as confounders for rejection diagnoses using dd-cfDNA.
Assuntos
Ácidos Nucleicos Livres , Aloenxertos , Biomarcadores , Estudos de Coortes , Rejeição de Enxerto , Humanos , Doadores de TecidosRESUMO
OBJECTIVES: We investigated to which extent disturbances in mineral metabolism predict 90-day clinical outcome in end-stage heart failure patients. DESIGN: Among numerous biochemical parameters, we measured serum levels of sodium and magnesium, the calciotropic hormones parathyroid hormone and 1,25-dihydroxyvitamin D as well as fibroblast growth factor-23 (a phosphaturic hormone) in 305 cardiac transplant candidates. Primary endpoint was a composite of the need of mechanical circulatory support (MCS), transplantation, or death. RESULTS: Of the study cohort, 33.4% reached the primary endpoint. In detail, 19% were transplanted (the vast majority was listed "high urgent"), 8.8% died and 5.6% received MCS implants. As determined by logistic regression analysis, all aforementioned biochemical parameters were independently related to the primary endpoint. Results did not change substantially when transplanted patients were censored. A risk score (0-5 points) was developed. Of the patients who scored 5 points 89.5% reached the primary endpoint whereas of the patients with a zero score only 3.8% reached the primary endpoint. CONCLUSIONS: Our data demonstrate that in addition to the well-known predictive value of disturbed sodium metabolism, derangements in calcium, phosphate, and magnesium metabolism also predict midterm clinical outcome in end-stage heart failure patients.
Assuntos
Insuficiência Cardíaca/sangue , Doenças Metabólicas/sangue , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Alemanha , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Transplante de Coração , Coração Auxiliar , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Magnésio/sangue , Masculino , Doenças Metabólicas/mortalidade , Doenças Metabólicas/terapia , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Projetos Piloto , Prognóstico , Medição de Risco , Fatores de Risco , Sódio/sangue , Fatores de Tempo , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
AIMS: Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). The purpose of the Catheter Ablation for atrial fibrillation in patientS with end-sTage heart faiLure and Eligibility for Heart Transplantation (CASTLE-HTx) trial is to test the hypothesis that atrial fibrillation (AF) ablation has beneficial effects on mortality and morbidity during 'waiting time' for heart transplantation (HTx) or to prolong the time span until LVAD implantation. METHODS AND RESULTS: CASTLE-HTx is a randomized evaluation of ablative treatment of AF in patients with severe left ventricular dysfunction who are candidates and eligible for HTx. The primary endpoint is the composite of all-cause mortality, worsening of HF requiring a high urgent transplantation, or LVAD implantation. The secondary study endpoints are all-cause mortality, cardiovascular mortality, cerebrovascular accidents, worsening of HF requiring unplanned hospitalization, AF burden reduction, unplanned hospitalization due to cardiovascular reason, all-cause hospitalization, quality of life, number of delivered implantable cardioverter defibrillator therapies, time to first implantable cardioverter defibrillator therapy, number of device-detected ventricular tachycardia/ventricular fibrillation episodes, left ventricular function, exercise tolerance, and percentage of right ventricular pacing. Ventricular myocardial tissue will be obtained from patients who will undergo LVAD implantation or HTx to assess the effect of catheter ablation on human HF myocardium. CASTLE-HTx will randomize 194 patients over a minimum time period of 2 years. CONCLUSIONS: CASTLE-HTx will determine if AF ablation has beneficial effects on mortality in patients with end-stage HF who are eligible for HTx.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Transplante de Coração , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Insuficiência Cardíaca/complicações , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
AIMS: Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions. METHODS AND RESULTS: We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively. CONCLUSIONS: Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.
Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Coração , Coração Auxiliar , Adulto , Pré-Escolar , Transplante de Coração/métodos , Humanos , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND Left ventricular assist device (LVAD) implantation may improve kidney function, but in patients awaiting heart transplantation, the long-term effects of LVAD implantation on renal function and subsequent clinical outcome are unclear. MATERIAL AND METHODS We analyzed data in patients with LVAD implants (n=139) and without LVAD implants (n=1038) who were listed for a heart transplant at our institution between 2000 and 2019. The primary endpoint was an impairment in renal function (decrease of creatinine-based estimated glomerular filtration rate [eGFR] by ≥30%) up to a maximum of 2 years after listing. Secondary endpoints were chronic kidney disease stage 4 or 5, heart transplantation, survival during listing, and 1-year survival after transplantation. RESULTS Values for eGFR increased after LVAD implantation (P=0.001) and were higher at the time of waitlisting in the LVAD group than in the non-LVAD group (P=0.002), but were similar between groups at the end of waitlisting (P=0.75). Two-year freedom from renal impairment was 50.6% and 66.7% in the LVAD and non-LVAD groups, respectively, with a multivariable-adjusted hazard ratio for the LVAD versus the non-LVAD group of 1.78 (95% confidence interval 1.19-2.68; P=0.005). Two-year freedom from chronic kidney disease stages 4-5 was similar between study groups (LVAD group: 83.5%; non-LVAD group: 80.1%; =0.50). The 2-year probability of transplantation was slightly lower in the LVAD group than in the non-LVAD group (50.0% and 55.8%, respectively, P=0.017). However, 2-year survival on the waiting list and 1-year survival after transplantation did not differ significantly between study groups (P-values >0.20). CONCLUSIONS Our data indicate a transient improvement in creatinine-based eGFR values by LVAD implantation without influencing survival.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Rim , Adulto , Feminino , Insuficiência Cardíaca/cirurgia , Humanos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
AIMS: Vitamin D supplementation is widely used in the clinical setting, but its effects on mortality and cardiovascular outcomes in patients with heart failure are unclear. This paper reports outcome data that were collected during follow-up of 3 years after closure of the EVITA trial (a 3 year randomized, placebo-controlled, intervention study with 4000 IU vitamin D daily in patients with advanced heart failure), to capture potential latency effects of vitamin D supplementation on clinical outcomes. METHODS AND RESULTS: The prespecified primary endpoint was overall mortality. Secondary endpoints included hospitalization, mechanical circulatory support implantation, high urgent listing for heart transplantation, and heart transplantation. For group comparisons, we used Cox regression models with a time-dependent categorical covariate. The calculated net difference in circulating 25-hydroxyvitamin D between the vitamin D and placebo groups dropped from 60.9 nmol/L at the end of the active study period to 3.2 nmol/L at the end of the post-intervention period. During the entire 6 year period, 73 patients (36.5%) died in the placebo group and 76 (38.8%) in the vitamin D group. Out of these 149 patients, 36 and 39 died during the first 3 years, and 37 and 37 during the second 3 years, respectively. The hazard ratio (HR) for mortality in the vitamin D versus the placebo group was 1.06 [95% confidence interval (CI): 0.68-1.66] for the first 3 years and 1.07 (95% CI: 0.68-1.70) for the 3 year post-intervention follow-up. Compared with the placebo group, the HRs for hospitalization and for mechanical circulatory support implant were significantly higher in the vitamin D group during vitamin D supplementation (HR = 1.31, 95% CI: 1.01-1.68 and HR = 2.01, 95% CI: 1.08-3.76, respectively) but not after vitamin D discontinuation (HR = 1.10, 95% CI: 0.62-1.94 and HR = 0.99, 95% CI: 0.38-2.56, respectively). There was no significant time-dependent effect on the risk of high urgent listing for heart transplantation and heart transplantation. CONCLUSIONS: No beneficial latency effects of vitamin D supplementation on overall mortality could be demonstrated. Instead, the disappearance of unfavourable findings in the vitamin D group (higher HRs for hospitalization and for mechanical circulatory support implant) after vitamin D discontinuation supports the assumption of adverse vitamin D effects on the cardiovascular system at doses of 4000 IU daily.
RESUMO
BACKGROUND: Vitamin D receptor knockout mice develop typical signs of congestive heart failure (CHF). In approximately 20% of stable CHF patients, frankly low concentrations of the vitamin D hormone calcitriol are found. AIMS: We investigated whether serum calcitriol concentrations predict clinical outcome in end-stage CHF. METHODS AND RESULTS: We collected blood samples in 383 end-stage CHF patients who were on a waiting list for cardiac transplantation. We assessed associations of calcitriol with disease severity and freedom from event (death or cardiac transplantation) during 1-year follow-up. In electively listed patients (n=325), 31% had deficient calcitriol levels (<43 pmol/l) compared to 47% in urgently/high urgently listed patients (n=58; P<0.001). As determined by multivariable logistic regression, calcitriol was an independent predictor of the listing status 'urgent/high urgent' (P<0.001). Calcitriol concentrations were also significantly lower in patients with an event (n=233) compared to those who survived on the waiting list (P<0.001). Cox regression analysis revealed that patients in the highest calcitriol tertile had a hazard ratio (95% CI) for an event of 0.506 (0.334-0.767) compared with patients in the lowest calcitriol tertile (P=0.005), after adjustment for potential confounders. CONCLUSION: Data indicate that low serum calcitriol concentrations are independently associated with poor clinical outcome in end-stage CHF.
Assuntos
Calcitriol/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Estudos Transversais , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: As waiting times for a heart transplant (HTx) increase, the decision of whether a patient should have a high urgent (HU) listing or mechanical circulatory support becomes crucial for further prognosis. The aim of this study was to determine the characteristics that predict failure of an HU listing (death/delisting due to urgent mechanical circulatory support implant or poor clinical condition), the 5-year survival rate, the 1-year post-transplant survival rate and the prognostic accuracy of the cardiac allocation score of patients on the HU list. METHODS: A total of 447 patients who were on the HU list at our institution between 2005 and 2016 were analysed and stratified according to occurrence of therapy failure or reception of an HTx. RESULTS: A total of 114 patients suffered from HU listing failure after a median HU time of 31.5 (15-69) days; 320 patients had a primary HTx after a median time of 51.5 (26-90) days on the HU list; 13 patients were excluded from data analysis because of an ongoing HU listing or delisting due to improvement in their haemodynamic condition. In multivariable logistic regression analysis, blood group 0 [odds ratio (OR) 2.48, 95% confidence interval (CI) 1.43-4.3; P = 0.001], INTERMACS Class 1 or 2 (OR 5.1, 95% CI 2.7-9.4; P < 0.001), vasoactive inotropic score (OR 1.18, 95% CI 1.09-1.27; P < 0.001) and brain natriuretic peptide levels (OR 1.00, 95% CI 1.00-1.00; P = 0.001) were identified as independent predictors of HU listing failure. Cardiac allocation score was not independently associated with listing failure. Estimated 5-year and 1-year post-HTx survival rates were similar in the primary HTx group and in patients receiving an HTx after HU therapy failure (P = 0.48 and P = 0.7, respectively). CONCLUSIONS: INTERMACS levels 1 and 2 and vasoactive inotropic score were the strongest predictors of HU listing failure.
Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Listas de Espera , Adulto , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca/mortalidade , Coração Auxiliar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida/tendências , Falha de TratamentoRESUMO
BACKGROUND: Determination of cardiac output (CO) is essential in diagnosis and management of heart failure (HF). The gold standard to obtain CO is invasive assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is supposed as a new method of CO determination. However, a validation of this method in HF is pending and performed in the present study. METHODS: Patients with chronic-stable HF and reduced left ventricular ejection fraction (LVEF ≤ 45%; HF-REF) underwent right heart catheterization including TD. NPCA using the CNAP Monitor (V5.2.14, CNSystems Medizintechnik AG) was performed simultaneously. Three standardized TD measurements were compared with simultaneous auto-calibrated NPCA CO measurements. RESULTS: In total, 84 consecutive HF-REF patients were enrolled prospectively in this study. In 4 patients (5%), TD was not successful and for 22 patients (26%, 18 with left ventricular assist device), no NPCA signal could be obtained. For the remaining 58 patients, Bland-Altman analysis revealed a mean bias of + 1.92 L/min (limits of agreement ± 2.28 L/min, percentage error 47.4%) for CO. With decreasing cardiac index, as determined by the gold standard of TD, there was an increasing gap between CO values obtained by TD and NPCA (r = - 0.75, p < 0.001), resulting in a systematic overestimation of CO in more severe HF. TD-CI classified 52 (90%) patients to have a reduced CI (< 2.5 L/min/m2), while NPCA documented a reduced CI in 18 patients (31%) only. CONCLUSIONS: In HF-REF patients, auto-calibrated NPCA systematically overestimates CO with decrease in cardiac function. Therefore, to date, NPCA cannot be recommended in this cohort.
Assuntos
Determinação da Pressão Arterial/métodos , Débito Cardíaco , Dedos/irrigação sanguínea , Insuficiência Cardíaca/diagnóstico , Processamento de Sinais Assistido por Computador , Idoso , Pressão Arterial , Determinação da Pressão Arterial/normas , Calibragem , Cateterismo de Swan-Ganz , Doença Crônica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Padrões de Referência , Reprodutibilidade dos Testes , Volume Sistólico , Termodiluição , Função Ventricular EsquerdaRESUMO
OBJECTIVE: 1,25-Dihydroxyvitamin D (1,25([OH]2D) is considered to be a negative endogenous regulator of the renin-angiotensin-aldosterone system (RAAS), but the effect of vitamin D supplementation on the RAAS is inconclusive. DESIGN: In this prespecified secondary analysis of a randomized controlled trial, we assessed in 165 patients with heart failure (vitamin D group: n = 83; placebo group: n = 82) the effect of three years of vitamin D supplementation with 4000 IU daily on parameters of the RAAS (renin and aldosterone) and on circulating 1,25(OH)2D, plasma phosphate, and fibroblast growth factor (FGF)-23. We assessed age- and baseline-adjusted between-group differences at study termination. RESULTS: Almost all patients were under treatment with beta-blockers, inhibitors of the RAAS, and diuretics. Initially, the frequency of concentrations above the laboratory-specific reference range (renin: >23.9 mIU/L; aldosterone: >232 ng/L) in the vitamin D and placebo group was 87.7% and 92.7%, respectively (renin), and 24.1% and 32.5%, respectively (aldosterone). Vitamin D increased adjusted 1,25(OH)2D concentrations significantly (mean treatment effect and 95% CI: 18.3 pmol/L,7.3 to 29.3 pmol/L; P < 0.001) but had no significant effects on phosphate (0.18 mmol/L, -0.00 to 0.35 mmol/L; P = 0.051), FGF-23 (685 RU/mL, -213 to 1585 RU/mL; P = 0.134), renin (312 mIU/L, -279 to 902 ng/L; P = 0.298), or aldosterone (-0.19 ng/L, -5.09 to 4.70 ng/L; P = 0.938). Vitamin D supplementation was, however, associated with an increase in renin concentrations in the subgroup with baseline 25-hydroxyvitamin D below 30 nmol/L (n = 67; 1365 mIU/, 343 to 2386 mIU/L; P = 0.010). CONCLUSIONS: In patients with advanced heart failure treated according to evidence-based guidelines, vitamin D supplementation did not significantly influence parameters of the RAAS in the entire study cohort but was associated with an increase in plasma renin concentrations in the subgroup with low baseline 25-hydroxyvitamin D concentrations.
RESUMO
We have recently hypothesized that low vitamin D status may contribute to the pathogenesis of congestive heart failure (CHF). This study was aimed at evaluating, in a pilot study, whether CHF patients have indications for a low vitamin D status during earlier periods of their lives. We performed a case-controlled study in 150 CHF patients and 150 controls. Study participants had to answer a questionnaire that included several items concerning vitamin D-associated lifestyle factors during childhood, adolescence, and adulthood. A vitamin D score was constructed. This score takes into consideration that ultraviolet-B (UVB) exposure is the major vitamin D source for humans and that those lifestyle factors, which are associated with regular UVB exposure, can guarantee an adequate vitamin D status at best. The vitamin D score was significantly higher in controls than in patients (p < 0.001). Compared with the controls, more patients lived in large cities (p < 0.001), fewer patients were members of a sport club (p < 0.001), and fewer patients had summer holidays every year (p < 0.01). Patients also reported significantly less alcohol consumption during adulthood than controls (p < 0.001). Our results demonstrate that CHF patients and controls differed in several vitamin D-associated lifestyle factors and in alcohol consumption during earlier periods of their lives.
Assuntos
Insuficiência Cardíaca/metabolismo , Estilo de Vida , Deficiência de Vitamina D/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Projetos Piloto , Estudos Retrospectivos , Fatores Socioeconômicos , Esportes , Luz Solar , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Identifying patients at risk for impaired long-term survival after heart transplantation (HT) remains a clinical challenge. The aim of this analysis was to investigate whether the gene expression profiling test AlloMap® is related to long-term survival after HT. METHODS: 46 patients who underwent HT between 2006 and 2007 who were originally included into the CARGO II trial at our institution were investigated. Patients were divided in two groups according to an increase or decrease of the AlloMap® score between 6 and 9months after HT. The primary endpoint of this study was long-term all-cause mortality. RESULTS: 23 patients showed an increase of the AlloMap® score between 6 and 9months after HT whereas the remaining 23 patients presented with a decrease of the score. After a median follow-up time of 8.1years (interquartile range 7.6-8.6), all-cause mortality was significantly elevated in patients with an AlloMap® increase compared with patients who showed a decrease of the score (log-rank p=0.005). A ratio of the AlloMap® at 9months to 6months of 1.02 or less was associated with a negative predictive value for all-cause mortality of 100%. CONCLUSIONS: Dynamic changes of the AlloMap® score between 6 and 9months after HT were strongly related to all-cause long-term survival after HT. These results suggest that AlloMap® potentially displays a useful tool to estimate the patients' risk for long-term mortality.
Assuntos
Regulação da Expressão Gênica , Insuficiência Cardíaca , Transplante de Coração , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de SobrevidaRESUMO
Everolimus has recently received approval for immunosuppressive therapy in heart transplant recipients in Austria and Germany. At our heart center we have treated 114 patients with everolimus since January 2004. Here we describe 6 cases of lingual angioedema (corresponding to 5.3% of the patients). Symptoms occurred within 2 to 41 days after initiation of therapy. In 5 out of the 6 patients, lingual angioedema disappeared with anti-allergic treatment alone. However, in one patient, two severe recurrent episodes of lingual angioedema occurred so that therapy had to be discontinued. We conclude that the potentially life-threatening condition of lingual angioedema should be considered a severe drug reaction after initiation of everolimus therapy in heart transplant recipients.
Assuntos
Angioedema/induzido quimicamente , Transplante de Coração/imunologia , Terapia de Imunossupressão/efeitos adversos , Sirolimo/análogos & derivados , Sirolimo/efeitos adversos , Sirolimo/farmacologia , Angioedema/patologia , Everolimo , HumanosRESUMO
The mTOR inhibitor everolimus (EVL) can be used for calcineurin inhibitor-sparing immunosuppression in heart transplantation (HTx). However, comparable data regarding clinical outcomes in HTx recipients receiving EVL either with dosage reduction of cyclosporine A (CSA) or with dosage reduction of tacrolimus (TAC) is scarce. In a retrospective data analysis, we compared 5-year clinical outcomes in 154 maintenance patients receiving EVL with CSA (n=106) or TAC (n=48). The primary endpoint was a composite of death, graft loss and EVL discontinuation (treatment failure). Secondary endpoints were kidney function, cardiac rejection, cytomegalovirus infection and biochemical safety parameters. In the CSA and TAC group, the primary endpoint was reached by 59.8% and 53.1%, respectively (P=0.716). Five-year mortality was 30.4% (CSA group) and 23.13% (TAC group), respectively (P=0.371), and freedom from EVL discontinuation was 53.3% and 59.6% (P=0.566) in the respective groups. Covariate-adjusted relative risk of treatment failure was in the CSA group=1.28 (95% CI: 0.70-2.34; P=0.43) compared with the TAC group. The course of covariate-adjusted estimated glomerular filtration rate and freedom from cytomegalovirus infection was similar in the two groups (P=0.502 and P=0.476), whereas covariate-adjusted freedom from rejection was lower in the CSA group compared with the TAC group (P=0.023). Lipid status and blood cell counts were comparable between groups. In conclusion, data indicate that EVL plus reduced TAC is not superior to EVL plus reduced CSA regarding treatment failure and kidney function. However, compared with EVL plus reduced CSA, EVL plus reduced TAC seems to reduce cardiac rejections.