A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) ...recipients are lacking.
We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes.
During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval CI, 9.7-16.3), 8.4 (95% CI, 6.0-11.4), and 7.0 (95% CI 4.8-9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9-67.1) and 8.7 (95% CI 6.2-11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2-60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients.
VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode.
Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart ...failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.
Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.
Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.
Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.
Summary
We conducted an observational study of 30 heart transplant recipients with serum low‐density lipoprotein cholesterol (LDL‐c) >100 mg/dl despite previous statin therapy, who were treated with ...rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long‐term rosuvastatin therapy beyond this 12‐week period were reviewed in February 2015. Over the 12‐week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL‐c and the ratio TC/high‐density lipoprotein cholesterol (HDL‐c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL‐c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL‐c, hepatic enzymes, bilirubin, or CPK. Twenty‐seven (90%) patients continued on long‐term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.
Aims
Maximum oxygen uptake (VO2max) is an essential parameter to assess functional capacity of patients with heart failure (HF). We aimed to identify clinical factors that determine its value, as ...they have not been well characterized yet.
Methods
We conducted a retrospective, observational, single‐centre study of 362 consecutive patients with HF who underwent cardiopulmonary exercise testing (CPET) as part of standard clinical assessment since 2009–2019. CPET was performed on treadmill, according to Bruce's protocol (n = 360) or Naughton's protocol (n = 2). We performed multivariable linear regression analyses in order to identify independent clinical predictors associated with peak VO2max.
Results
Mean age of study patients was 57.3 ± 10.9 years, mean left ventricular ejection fraction was 32.8 ± 14.2%, and mean VO2max was 19.8 ± 5.2 mL/kg/min. Eighty‐nine (24.6%) patients were women, and 114 (31.5%) had ischaemic heart disease. Multivariable linear regression analysis identified six independent clinical predictors of VO2max, including NYHA class (B coefficient = −2.585; P < 0.001), age (B coefficient per 1 year = −0.104; P < 0.001), tricuspid annulus plane systolic excursion (B coefficient per 1 mm = +0.209; P < 0.001), body mass index (B coefficient per 1 kg/m2 = −0.172; P = 0.002), haemoglobin (B coefficient per 1 g/dL = +0.418; P = 0.007) and NT‐proBNP (B coefficient per 1000 pg/mL = −0.142; P = 0.019).
Conclusions
The severity of HF (NYHA class, NT‐proBNP) as well as age, body composition and haemoglobin levels influence significantly exercise capacity. In patients with HF, the right ventricular systolic function is of greater importance for the physical capacity than the left ventricular systolic function.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear.
Data were collected from 419 adult patients with ...clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders.
Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016).
Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.
Our aim was to assess the prognostic value of the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) scale in patients undergoing urgent heart transplantation (HT).
...Retrospective analysis of 111 patients treated with urgent HT at our institution from April, 1991 to October, 2009. Patients were retrospectively assigned to three levels of the INTERMACS scale according to their clinical status before HT.
Patients at the INTERMACS 1 level (n=31) more frequently had ischemic heart disease (P=.03) and post-cardiothomy shock (P=.02) than patients at the INTERMACS 2 (n=55) and INTERMACS 3-4 (n=25) levels. Patients at the INTERMACS 1 level showed higher preoperative catecolamin doses (P=.001), a higher frequency of use of mechanical ventilation (P<.001), intraaortic balloon (P=.002) and ventricular assist devices (P=.002), and a higher frequency of preoperative infection (P=.015). The INTERMACS 1 group also presented higher central venous pressure (P=.02), AST (P=.002), ALT (P=.006) and serum creatinine (P<.001), and lower hemoglobin (P=.008) and creatinine clearance (P=.001). After HT, patients at the INTERMACS 1 level had a higher incidence of primary graft failure (P=.03) and postoperative need for renal replacement therapy (P=.004), and their long-term survival was lower than patients at the INTERMACS 2 (log rank 5.1, P=.023; HR 3.1, IC 95% 1.1-8.8) and INTERMACS 3-4 level (log rank 6.1, p=0.013; HR 6.8, IC 95% 1.2-39.1).
Our results suggest that the INTERMACS scale may be a useful tool to stratify postoperative prognosis after urgent HT.
To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes.
Observational study ...based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden –as assessed by a rejection score–, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years.
Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV.
Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population.
Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.
•Soluble HLA-G levels decreased over the first year after HT.•No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV.•Higher HLA-G expression was associated with a higher frequency of infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Cancer incidence and cancer-related mortality of patients with heart failure are higher than those expected for the general population.•Increased sympathetic activity, renin-angiotensin-aldosterone ...system activation, chronic inflammation and oxidative stress are proposed biological mechanisms to explain the increased risk of cancer in patients with heart failure.•Prognosis of patients with heart failure and co-existing malignancies is poor, with mortality rates that exceed 40% during the first year after cancer diagnosis.
To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF).
Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory.
We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4–2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1–4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1–1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8–3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26).
Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Analizar la supervivencia de los pacientes con insuficiencia cardiaca (IC) tratados en una unidad especializada.
Estudio prospectivo de una cohorte de pacientes con IC tratados en una unidad ...especializada entre 2011 y 2017. Se comparó la mortalidad observada a 1 y 3 años con la mortalidad pronosticada por la puntuación de riesgo del Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC).
Se estudió a 1.280 pacientes, con una mediana de la puntuación MAGGIC de 19 intervalo intercuartílico, 13-24. Las tasas de prescripción de bloqueadores beta, inhibidores de la enzima de conversión de la angiotensina, antagonistas del receptor de la angiotensina II, antagonistas del receptor de mineralcorticoides y sacubitrilo-valsartán fueron del 93, el 67, el 22, el 73 y el 16% respectivamente. La puntuación MAGGIC mostró una discriminación adecuada de la mortalidad a 1 año (estadístico c=0,71) y a 3 años (estadístico c=0,76). La mortalidad observada fue significativamente menor que la pronosticada, tanto a 1 año (el 6,2 frente al 10,9%; cociente observada/pronosticada=0,57; p<0,001) como a 3 años (el 16,7 frente al 27,7%; cociente observada/pronosticada=0,60; p<0,001). Esta discrepancia se observó en diversos subgrupos, excepto en los pacientes mayores de 70 años (el 29,9 frente al 34,7%; cociente observada/pronosticada=0,86; p=0,126) y en pacientes con fracción de eyección> 40% (el 19,6 frente al 20,7%; cociente observada/pronosticada=0,95; p=0,640).
Los pacientes con IC tratados en una unidad especializada presentaron una mortalidad inferior a la pronosticada por la puntuación MAGGIC.
To analyze survival in heart failure (HF) patients treated at a specialized unit.
Prospective cohort-based study of HF patients treated at a specialized unit from 2011 to 2017. Observed 1- and 3-year mortality rates were compared with those predicted by the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score.
We studied 1280 patients, whose median MAGGIC risk score was 19 interquartile range, 13-24. Prescription rates of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and sacubitril-valsartan were 93%, 67%, 22%, 73%, and 16%, respectively. The MAGGIC risk score showed good discrimination for mortality at 1 year (c-statistic=0.71) and 3 years (c-statistic=0.76). Observed mortality was significantly lower than predicted mortality, both at 1 year (6.2% vs 10.9%; observed/predicted ratio=0.57; P<.001) and at 3 years (16.7% vs 27.7%; observed/predicted ratio=0.60; P<.001). This discrepancy was found in several subgroups, except in patients aged> 70 years (29.9% vs 34.7%; observed/predicted ratio=0.86; P=.126) and in patients with ejection fraction> 40% (19.6% vs 20.7%; observed/predicted ratio=0.95; P=.640).
Mortality in HF patients treated at a specialized clinic was significantly lower than that predicted by the MAGGIC risk score.