Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers ...use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.
Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine ...the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting.
Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies.
Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%).
The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases.
Abstract Background Pulmonary arterial hypertension (PAH) is common in patients with congenital heart disease (CHD). Although Eisenmenger syndrome may be on decline, other types of PAH–CHD are ...increasing and little is known on long-term outcome of this population. We report the PAH–CHD population of Spain via a national registry with focus on long-term survival. Methods and results A total of 240 consecutive patients (age 37.7 ± 14.1 years, 67.9% females) with PAH–CHD included in the REHAP registry were analysed. Patients were classified into 3 groups: 1) Eisenmenger syndrome, 2) postoperative-PAH and 3) PAH associated with small defects. Over a median follow-up time of 4.5 1.6–7.1 years, 50 patients (20.8%) died or underwent lung/heart-lung transplantation. Patients with Eisenmenger syndrome had better survival than postoperative-PAH (HR 0.1 95% CI: 0.2–0.9, p = 0.048) but no advantage compared to small defects (HR 4.4, 95% CI 0.6–31.4, p = 0.15). In the overall PAH–CHD population, patients in NYHA functional class III–IV had a 3-fold increased risk of death (HR 3.0, 95% CI: 1.5–5.9, p = 0.001). Amongst patients with Eisenmenger syndrome, a pre-tricuspid shunt had a 2.6-fold increase risk of death (HR 2.6, 95% CI: 1.2–5.6, p = 0.03). There was no significant difference in survival between patients with postoperative-PAH and patients with iPAH (HR 0.99 95% CI: 0.6–1.7, p = 0.97). Conclusion PAH–CHD is associated with mid to long-term mortality. Outcome relates closely to functional class, type of PAH–CHD and within the Eisenmenger cohort, with location of the shunt. Adults with postoperative-PAH have the worse prognosis in the PAH–CHD cohort, reinforcing the need for lifelong close follow-up of such patients.
While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the ...clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field’s incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.
Natural History and Prognostic Factors in Alcoholic Cardiomyopathy Guzzo-Merello, Gonzalo, MD, PhD; Segovia, Javier, MD, PhD; Dominguez, Fernando, MD ...
JACC. Heart failure,
2015, January 2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives This study sought to determine the natural history of contemporary alcoholic cardiomyopathy (ACM), to compare it with that of idiopathic dilated cardiomyopathy (IDCM), and to ...identify risk factors for poor outcome. Background ACM is a common cause of dilated cardiomyopathy (DCM), but little is known about its natural history or the effect of reducing alcohol intake on disease progression. Methods We studied the clinical characteristics and outcomes of 94 consecutive patients with ACM and 188 with IDCM, evaluated over the period between 1993 and 2011. Results After a median follow-up of 59 months (interquartile range: 25 to 107 months), 14 ACM patients (15%) had died from cardiovascular causes (6 from heart failure and 8 from sudden cardiac death), 14 (15%) underwent heart transplantation, 35 (37%) experienced recovery in left ventricular function, and 31 (33%) remained clinically stable without improvement in systolic function. Transplantation-free survival was higher in ACM patients than in IDCM patients (p = 0.002), and ACM was associated with a favorable outcome on multiple analysis of the entire cohort (odds ratio OR: 0.4; 95% confidence interval CI: 0.2 to 0.8; p = 0.01). Independent predictors of death or heart transplantation in ACM identified by multiple logistic regression analysis were atrial fibrillation (OR: 9.7; 95% CI: 2.56 to 36.79; p = 0.001); QRS duration >120 ms (OR: 7.2; 95% CI: 2.02 to 26; p = 0.002), and lack of beta-blocker therapy (OR: 4.4; 95% CI: 1.35 to 14.49; p = 0.014). ACM patients who reduced their alcohol intake to moderate levels exhibited similar survival (p = 0.22) and cardiac function recovery (p = 0.8) as abstainers. Conclusions ACM has a better prognosis than IDCM. Atrial fibrillation, QRS width >120 ms, and the absence of beta-blocker therapy identify patients with a poor outcome. Alcohol abstainers and those who reduce intake to a moderate degree show similar clinical outcomes.
Acute cellular rejection (ACR) is still a relevant complication after orthotopic heart transplantation. The diagnosis of ACR is based on endomyocardial biopsy (EMB). Recent advances in ...two-dimensional strain imaging may allow early noninvasive detection of ACR. The objective of this study was to analyze the usefulness of conventional and new echocardiographic parameters to exclude ACR after orthotopic heart transplantation.
Thirty-four consecutive adult heart transplant recipients admitted to a single center between January 2010 and December 2012 for orthotopic heart transplantation were prospectively included. A total of 235 pairs of EMB and echocardiographic examination were performed. A median of seven studies per patient (interquartile range, six to eight studies per patient) were performed during the first year of follow-up. Classic echocardiographic parameters; speckle-tracking-derived left ventricular (LV) longitudinal, radial, and circumferential strain; and global and free wall right ventricular (RV) longitudinal strain were analyzed.
ACR was detected in 26.4% of EMB samples (n = 62); 5.1% (n = 12) required specific treatment (ACR degree ≥ 2R). Lower absolute values of global LV longitudinal strain and free wall RV longitudinal strain were present in patients with ACR degree ≥ 2R compared with those without ACR (13.7 ± 2.7% vs 17.8 ± 3.4% and 16.6 ± 3.6% vs 23.3 ± 5.2%, respectively). An average LV longitudinal strain < 15.5% had 85.7% sensitivity, 81.4% specificity, 98.8% negative predictive value, 25.0% positive predictive value, and 81.7% accuracy for the presence of ACR degree ≥ 2R. Free wall RV longitudinal strain < 17% had 85.7% sensitivity, 91.1% specificity, 98.8% negative predictive value, 42.9% positive predictive value, and 90.7% accuracy for ACR degree ≥ 2R. Both variables were normal in 106 echocardiograms (57.6%); none of these patients presented with ACR degree ≥ 2R.
The combination of two new echocardiographic measures, global LV and RV free wall longitudinal strain, may be able to identify a group of heart transplant patients who are unlikely to have ACR. If these findings are confirmed independently, it may be possible to use LV and RV strain measures as reliable tools to exclude ACR and to reduce the burden of repeated EMB.
Reforming the individual income tax in Spain Guner, Nezih; López-Segovia, Javier; Ramos, Roberto
SERIEs : journal of the Spanish Economic Association,
12/2020, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Can the Spanish government generate more tax revenue by making personal income taxes more progressive? To answer this question, we build a life-cycle economy with uninsurable labor productivity risk ...and endogenous labor supply. Individuals face progressive taxes on labor and capital incomes and proportional taxes that capture social security, corporate income, and consumption taxes. Our answer is yes, but not much. A reform that increases labor income taxes for individuals who earn more than the mean labor income and reduces taxes for those who earn less than the mean labor income generates a small additional revenue. The revenue from labor income taxes is maximized at an effective marginal tax rate of 51.6% (38.9%) for the richest 1% (5%) of individuals, versus 46.3% (34.7%) in the benchmark economy. The increase in revenue from labor income taxes is only 0.82%, while the total tax revenue declines by 1.55%. The higher progressivity is associated with lower aggregate labor supply and capital. As a result, the government collects higher taxes from a smaller economy. The total tax revenue is higher if marginal taxes are raised only for the top earners. The increase, however, must be substantial and cover a large segment of top earners. The rise in tax collection from a 3 percentage points increase on the top 1% is just 0.09%. A 10 percentage points increase on the top 10% of earners (those who earn more than €41,699) raises total tax revenue by 2.81%.
The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years ...old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors.
We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors.
There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs. 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18-1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22-2.27; p = 0.001).
There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.
Prognosis of advanced cardiac light-chain amyloidosis (ACAL) is ominous. Diagnosis of ACAL is frequently preceded by several biopsies of non-clinically affected tissues, which can result in dangerous ...treatment delays. Combinations of alkylators and steroids have a limited role in its therapy. Definitive efficacy of bortezomib in ACAL is not widely described. In this study we analyze the diagnostic yield of biopsies and compare the effect of bortezomib with other therapeutic strategies in ACAL patients.
This study is a retrospective analysis of 40 consecutive ACAL patients treated at our hospital (2005 to 2015). For comparison purposes, the cohort was divided into 2 groups: patients treated with bortezomib (n = 23) and those treated with other therapeutic approaches (non-bortezomib, n = 8).
Sensitivity of biopsies of non-clinically affected organs was 23%, as compared with 97% for affected organ biopsies (p < 0.0001). The need for >2 biopsies resulted in an average delay in diagnosis of 4.1 months (p = 0.007). Hematologic response was observed in 96% of patients in the bortezomib group compared with 25% in the non-bortezomib group (relative risk = 3.8; 95% confidence interval 1.14 to 12.75; p = 0.0002). Cardiac response criteria were met by 60% of patients in the bortezomib group as compared with none in the non-bortezomib group (p = 0.005). Survival at 6 months and 1 and 2 years for bortezomib patients was 91%, 91% and 73%, as compared with 58%, 15% and 0% for non-bortezomib patients (log rank, p < 0.0001), respectively.
In our experience, the sensitivity of biopsies from non-affected organs in ACAL is poor and could result in diagnostic delay. Bortezomib was associated with higher hematologic and cardiac response rates as well as survival when compared with other therapies.
Primary graft failure (PGF) is the leading cause of early mortality after heart transplantation (HT). Our aim is to propose a working definition of PGF and to develop a predictive risk score.
PGF was ...defined by four criteria reflecting significant myocardial dysfunction, severe hemodynamic impairment, early onset after HT, and absence of secondary causes of graft dysfunction. We identified independent risk factors for PGF in a derivation series of 621 HTs and constructed a predictive model. After proving its internal consistency we tested the model in a prospective validation series.
The incidence and lethality of PGF in our series were 9% and 80%, respectively. We identified 6 multivariate risk factors for PGF (Right atrial pressure ≥ 10 mm Hg, recipient Age ≥ 60 years, Diabetes mellitus, Inotrope dependence, donor Age ≥ 30 years, Length of ischemic time ≥ 240 minutes--i.e., RADIAL). Analysis of isolated right ventricular failure showed similar predictors. The RADIAL score was obtained by adding 1 point for each of these factors present in a given HT. PGF incidence increased significantly as the RADIAL score increased (p < 0.001 for trend). Rates of actual and predicted PGF incidence for RADIAL subgroups showed a good correlation (C-statistic = 0.74). In a prospective validation cohort, RADIAL score kept its predictive ability.
PGF as defined by these criteria showed a high impact on early post-HT mortality in our series. The RADIAL score showed good ability to predict the development of PGF, and could be useful in the prevention and early treatment of this complication.
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