In pulmonary embolism (PE) without hemodynamic compromise, the prognostic value of right ventricular (RV) dysfunction as measured by echocardiography, computed tomography (CT) or biological ...(natriuretic peptides) markers has only been assessed in small studies.
Databases were searched using the combined medical subject headings for right ventricular dysfunction or right ventricular dilatation with the exploded term acute pulmonary embolism. This retrieved 8 echocardiographic marker based studies (n = 1249), three CT marker based studies (n = 503) and 7 natriuretic peptide based studies (n = 582). A meta-analysis of these data was performed with the primary endpoint of mortality within three months after pulmonary embolism, and a secondary endpoint of overall mortality and morbidity by pulmonary embolism.
Patients with PE without hemodynamic compromise on admission and the presence of RV dysfunction determined by echocardiography and biological markers were associated with increased short-term mortality (odds ratio (OR) ECHO = 2.36; 95% confidence interval (CI): 1.3-43; OR BNP = 7.7; 95% CI: 2.9-20) while CT was not (ORCT = 1.54-95% CI: 0.7-3.4). However, corresponding pooled negative and positive likelihood ratios independent of death rates were unsatisfactory for clinical usefulness in risk stratification.
The presence of echocardiographic RV dysfunction or elevated natriuretic peptides is associated with short-term mortality in patients with pulmonary embolism without hemodynamic compromise. In contrast, the prognostic value of RV dilation on CT has yet to be validated in this population. As indicated both by positive and negative likelihood ratios the current prognostic value in clinical practice remains very limited.
Late antibody-mediated rejection (AMR) after heart transplantation is suspected to be associated with a poor short-term prognosis.
A retrospective single-center observational study was performed. ...Late AMR was defined as AMR occurring at least 1 year after heart transplantation. The study included all consecutive patients with proven and treated late acute AMR at the authors' institution between November 2006 and February 2013. The aim was to analyze the prognosis after late AMR, including mortality, recurrence of AMR, left ventricular ejection fraction, and cardiac allograft vasculopathy (CAV). Selected endomyocardial biopsy specimens obtained before AMR were also blindly reviewed to identify early histologic signs of AMR.
The study included 20 patients treated for late AMR. Despite aggressive immunosuppressive therapies (100% of patients received intravenous methylprednisolone, 90% received intravenous immunoglobulin IVIg,85% received plasmapheresis, 45% received rituximab), the prognosis remained poor. Survival after late AMR was 80% at 1 month, 60% at 3 months, and 50% at 1 year. All early deaths (<3 months, n = 8) were directly attributable to graft dysfunction or to complication of the intense immunosuppressive regimen. Among survivors at 3 months (n = 12), histologic persistence or recurrence of AMR, persistent left ventricular dysfunction, and fulminant CAV were common (33%, 33%, and 17% of patients). Microvascular inflammation was detected in at least 1 biopsy specimen obtained before AMR in 13 patients (65%).
Prognosis after late AMR is poor despite aggressive immunosuppressive therapies. Fulminant CAV is a common condition in these patients. Microvascular inflammation is frequent in endomyocardial biopsy specimens before manifestation of symptomatic AMR.
Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant ...recipients. We performed a single‐center, single‐arm, open‐label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor‐specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody‐mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy‐proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk.
ClinincalTrials.gov, NCT02013037.
Complement inhibition in the early posttransplant period after immunologically high‐risk heart transplantation is well tolerated and associated with a dramatic decrease in the risk of biopsy‐proven antibody‐mediated rejection.
Despite major advances in immunosuppression, allograft rejection remains an important complication after heart transplantation, and it is associated with increased morbidity and mortality. The gold ...standard invasive strategy to monitor and diagnose cardiac allograft rejection, based on the pathologic evaluation of endomyocardial biopsies, suffers from many limitations including the low prevalence of rejection, sample bias, high inter-observer variability, and international working formulations based on arbitrary cut-offs that simplify the landscape of rejection. The development of innovative diagnostic and prognostic strategies—integrating conventional histology, molecular profiling of allograft biopsy, and the discovery of new tissue or circulating biomarkers—is one of the major challenges of translational medicine in solid organ transplantation, and particularly in heart transplantation. Major advances in the field of biomarkers of rejection have paved the way for a paradigm shift in the monitoring and diagnosis of cardiac allograft rejection. We review the recent developments in the field, including non-invasive biomarkers to minimize the number of protocol endomyocardial biopsies and tissue biomarkers as companion tools of pathology to refine the diagnosis of cardiac rejection. Finally, we discuss the potential role of these biomarkers to provide an integrated bio-histomolecular diagnosis of cardiac allograft rejection.
Femoral arterial access site complications are responsible for a substantial proportion of the bleeding complications that occur in patients undergoing percutaneous coronary intervention (PCI). ...Because bleeding is associated with an increase in morbidity and mortality, pharmacologic and nonpharmacologic strategies associated with lower bleeding risk may improve outcomes. From this perspective, radial artery access, which is associated with a similar rate of success as femoral artery access with lower rates of bleeding, might become the “gold standard” for PCI. Although transradial technique requires a specific skill set and significant learning curve, success rates comparable to those of the femoral approach may be achieved. The benefits of radial access may be further enhanced by using antithrombotic strategies that maintain efficacy but limit bleeding risk. Indeed, a substantial proportion of bleeding complications unrelated to the access site occur, a finding that supports the use of safer antithrombotic regimens to optimize patient outcomes.
The relationship between brain natriuretic peptide (BNP) increase in acute pulmonary embolism (PE) and the increase in mortality and morbidity has frequently been suggested in small studies but its ...global prognostic performance remains largely undefined. We performed a systematic review and meta-analysis of data to examine the prognostic value of elevated BNP for short-term all-cause mortality and serious adverse events.
The authors reviewed PubMed, BioMed Central, and the Cochrane database and conducted a manual review of article bibliographies. Using a prespecified search strategy, we included a study if it used BNP or N-terminal pro-BNP biomarkers as a diagnostic test in patients with documented PE and if it reported death, the primary endpoint of the meta-analysis, in relation to BNP testing. Studies were excluded if they were performed in patients without certitude of PE or in a subset of patients with cardiogenic shock. Twelve relevant studies involving a total of 868 patients with acute PE at baseline were included in the meta-analysis using a random-effects model.
Elevated BNP levels were significantly associated with short-term all-cause mortality (odds ratio OR 6.57, 95% confidence interval CI 3.11 to 13.91), with death resulting from PE (OR 6.10, 95% CI 2.58 to 14.25), and with serious adverse events (OR 7.47, 95% CI 4.20 to 13.15). The corresponding positive and negative predictive values for death were 14% (95% CI 11% to 18%) and 99% (95% CI 97% to 100%), respectively.
This meta-analysis indicates that, while elevated BNP levels can help to identify patients with acute PE at high risk of death and adverse outcome events, the high negative predictive value of normal BNP levels is certainly more useful for clinicians to select patients with a likely uneventful follow-up.
Background
Sensitized patients, i.e. recipients with preformed donor-specific HLA antibodies (pfDSA), are at high-risk of developing antibody-mediated rejections (AMR) and dying after heart ...transplantation (HTx). Perioperative desensitization procedures are associated with better outcomes but can cause sensitization, which may influence their efficacy.
Methods
In sensitized patients (pfDSA>1000 mean immunofluorescence (MFI) units), we assessed the effect of perioperative desensitization by comparing treated patients to a historical control cohort. Multivariable survival analyses were performed on the time to main outcome, a composite of death and biopsy-proven AMR with 5-year follow-up.
Results
The study included 68 patients: 31 control and 37 treated patients. There was no difference in preoperative variables between the two groups, including cumulative pfDSA 4026 (1788;8725)
vs
4560 (3162;13392) MFI units,
p
=0.28. The cause of sensitization was pregnancy in 24/68, 35.3%, transfusion in 61/68, 89.7%, and previous HTx in 4/68, 5.9% patients. Multivariable analysis yielded significant protective association between desensitization and events (adjusted (adj.) hazard ratio (HR)=0.44 (95% confidence interval (95CI)=0.25-0.79),
p
=0.006) and deleterious association between cumulative pfDSA and events per 1000-MFI increase, adj.HR=1.028 (1.002-1.053), p=0.031. There was a sex-difference in the efficacy of desensitization: in men (n=35), the benefit was significant unadj.HR=0.33 (95CI=0.14-0.78); p=0.01, but not in women (n=33) unadj.HR=0.52 (0.23-1.17), p=0.11. In terms of the number of patients treated, in men, 2.1 of patients that were treated prevented 1 event, while in women, 3.1 required treatment to prevent 1 event.
Conclusion
Perioperative desensitization was associated with fewer AMR and deaths after HTx, and efficacy was more pronounced in men than women.
The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients ...awaiting heart transplantation (HT).
All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002 and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05).
A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.
Aims
The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non‐inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We ...aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist.
Methods and results
All non‐inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The ‘warm‐dry’, ‘cold‐dry’, ‘warm‐wet’, and ‘cold‐wet’ profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the ‘warm‐dry’ category as reference, a significant increase in the risk of primary outcome was observed only in the ‘wet’ categories, irrespectively of ‘warm/cold’ status: hazard ratios, 1.50; 1.06–2.13; P = 0.024 in ‘warm‐wet’ and 1.77; 1. 25–2.49; P = 0.001 in ‘cold‐wet’.
Conclusions
Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. ‘Wet’ patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.
Background Single center studies using serial cerebral diffusion-weighted magnetic resonance imaging in patients having cardiac catheterization have suggested that cerebral microembolism might be ...responsible for silent cerebral infarct (SCI) as high as 15% to 22%. We evaluated in a multicenter trial the incidence of SCIs after cardiac catheterization and whether or not the choice of the arterial access site might impact this phenomenon. Methods and Results Patients were randomized to have cardiac catheterization either by Radial (n = 83) or Femoral (n = 77) arterial approaches by experimented operators. The main outcome measure was the occurrence of new cerebral infarct on serial diffusion-weighted magnetic resonance imaging. Patient and catheterization characteristics, including duration of catheterization, were similar in both groups. The risk of SCI did not differ significantly between the Femoral and Radial groups (incidence of 11.7% versus 17.5%; OR, 0.85; 95% CI, 0.62-1.16; P = .31). At multivariable analysis, the independent predictors of SCI were the patient's higher height and lower transvalvular gradient. Conclusions The high rate of SCI after cardiac catheterization of patients with aortic stenosis was confirmed, but its occurrence was not affected by the selection of Radial and Femoral access.
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