By removing the main source of the mutated TTR, liver transplantation (LT) has become the standard treatment for ATTR (1). Because the demand for liver grafts exceeds the number of available organs ...and because new treatments have recently emerged, screening patients at high risk of death after LT is critical (2). The risk score was built from variables that measured the cardiac and neurological status regardless of mutation type. ...our proposed score should be useful to gauge the risk of patients with rare variants of TTR and to take into account the phenotypic variability encountered among patients with a similar mutation.
By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared ...these two therapeutic strategies.
In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score).
345 patients treated with tafamidis (n = 129) or LT (n = 216) were analyzed, and 144 patients were matched (72 patients in each group, median age 54 years, 60% carrying the V30M mutation, 81% of stage I, 69% with cardiac involvement, median follow-up: 68 months). Patients treated with tafamidis had longer survival than LT patients (HR: 0.35; p = .032). Conversely, they also presented a 3.0-fold higher risk of cardiac worsening and a 7.1-fold higher risk of neurological worsening (p = .0071 and p < .0001 respectively).
ATTRv amyloidosis patients treated with tafamidis would present a better survival but also a faster deterioration of their cardiac and neurological statuses as compared with LT. Further studies are needed to clarify the therapeutic strategy in ATTRv amyloidosis.
Amyloid neuropathies of acquired or genetic origin are disabling and life-threatening, until recently there were few treatment options available. Poor prognosis is related to progressive neuropathy ...and associated, although often underdiagnosed, cardiac involvement in specific transthyretin (TTR) gene mutations. Recent progress has modified prognosis and management of amyloid neuropathies. In TTR-familial amyloidosis with polyneuropathy, major changes have occurred over the last 30 years: better knowledge concerning genetics, phenotypes and epidemiology, and the advent of possible treatments. Liver transplantation, first performed in 1990, stopped disease progression, thus doubling survival in early onset V30M patients. More recently tetramer stabilizers (Tafamidis and Diflunisal) showed a significant reduction of progression of neuropathic scores; Tafamidis is now recommended in Stage I patients. Two multicentric clinical trials are now ongoing to evaluate TTR gene silencing by antisense Oligonucleotides (ASO) or siRNA. In the near future we should have new therapeutical options for patients with amyloid neuropathy.
Background: Hereditary transthyretin amyloidosis (ATTR) is a multisystemic disease involving mainly the peripheral nervous system and the heart. Liver transplantation (LT) is the reference treatment ...for ATTR neuropathy and preoperative detection of high risk patients is crucial. We aimed to document the causes of death of ATTR patients after LT, their temporal trends, and to evaluate whether the available preoperative tools that predict the risk of death after LT for hereditary ATTR amyloidosis matched with these trends.
Methods: A retrospective longitudinal cohort study was performed on 215 consecutive ATTR patients who underwent LT between January 1993 and January 2011. Each patient's death cause and timing were classified.
Results: Over a median follow up of 5.9 years, 84 patients died. The rate of death was higher in the first year following LT than thereafter (13.0 vs. 4.3 ± 1.8%/year; p = .004). Cardiac events ranked as the leading cause of death (C: 38%), followed by infections (I: 24%), graft complications (G: 17%), end stage amyloidosis, stroke and others (ASO: 7% each). Deaths due to graft complications and infections (GI) occurred earlier than those due to end stage amyloidosis and stroke. Death prediction was less accurate for GI-related mortality than for other causes, which blunted the accuracy of the early-term risk prediction scores.
Conclusions In ATTR amyloidosis, cardiac events were the leading cause of death after liver transplantation. Close preoperative evaluation allowed for accurate mid-term prediction of mortality, but the high rate of graft complications and infections blunted the early-term risk prediction.
Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, ...comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited.
To compare ischaemic and bleeding risks across the major c-DESs used in France.
French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics.
A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 95% confidence interval 0.68–1.07 and 1.04 95% confidence interval 0.98–1.10 compared with XIENCE® used as the reference) and when each outcome was considered separately.
In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.
Les stents actifs (DES) diminuent la survenue d’évènements ischémiques, mais peuvent entraîner des thromboses et des hémorragies secondaires au traitement antiagrégant plaquettaire. Les données d’efficacité et de sécurité comparant les DES en vie réelle sont limitées.
Cette étude avait pour objectif de comparer les risques ischémiques et hémorragiques entre les DES couramment utilisés dans la pratique française.
Les données utilisées sont issues du Système national des données de santé. Les patients implantés de DES en 2014 ont été suivis pendant un an. Les risques d’évènements ischémiques (regroupant nouvelle revascularisation, infarctus du myocarde et/ou accident vasculaire cérébral), d’évènements hémorragiques majeurs et de décès ont été comparés entre XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® et ORSIRO®, à l’aide d’un modèle de Cox multiniveaux ajusté sur les caractéristiques des patients et des centres implanteurs à l’inclusion.
Au total, 52 891 patients étaient inclus : 34,4 % recevaient XIENCE® ; 27,6 % PROMUS® ; 24,0 % RESOLUTE® ; 8,0 % BIOMATRIX® ; 5,0 % NOBORI® ; et 1,0 % ORSIRO®. Parmi eux, 9378 présentaient au moins un évènement (ischémique, 6064 ; hémorragique, 1968 ; décès, 2411), avec une incidence de 19 pour 100 personnes-années. En analyse multivariée, le risque global ne différait entre les DES (HRs ajusté entre 0,85 IC 95 % 0,68–1,07 et 1,04 IC 95 % 0,98–1,10 comparé à XIENCE®) et également pour chaque évènement considéré séparément.
En vie réelle, les risques ischémiques et hémorragiques ne diffèrent pas entre les DES jusqu’à un an après l’implantation. D’autres études en pratique clinique sont nécessaires pour comparer l’efficacité et la sécurité à long terme entre les DES.
Purpose of Review
Nuclear imaging recently gained a key role in the diagnosis and prognostic assessment of transthyretin (TTR)-related cardiac amyloidosis. This review aims at summarizing the ...state-of-the art regarding the implementation of nuclear imaging in the management of hereditary mutated TTR-cardiac amyloidosis (mTTR-CA).
Recent Findings
Although cardiac uptake of bone tracers is acknowledged as a specific marker of TTR amyloid cardiac burden, recent studies validated the implementation of bone scan in the flow chart for non-invasive diagnosis and follow-up of CA in multicenter trials. Simultaneously, cardiac denervation evidenced by MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in mTTR-CA.
Summary
By its unique ability to assess both amyloid burden and cardiac denervation, nuclear imaging may prove useful as part of multimodality imaging tools to trigger treatment initiation and monitoring in patients with mTTR-CA.
Recent data have reported that neoatherosclerosis could develop long after stent implantation and lead to subsequent rupture and acute coronary syndrome (ACS). We sought to identify the presence of ...in-stent neoatheroma (ISNA) in patients with very late stent thrombosis (VLST) using optical coherence tomography (OCT).
All patients from two catheterization centres who presented with ACS related to VLST underwent a standard coronary angiography and intra-coronary OCT. ISNA was defined as the combination of diffuse neointimal proliferation, lipid-laden intima with plaque organization, and fibrous cap rupture with no evidence of an uncovered strut. Out of 2139 ACS patients, 20 presented with definite VLST, including 10 with evidence of ISNA lesions, detected using OCT. The mean delay between initial percutaneous coronary intervention and VLST was longer in the ISNA patients compared with non-ISNA patients (10.5 ± 1.6 vs. 4.0 ± 0.6 years, P = 0.003). The mean LDL-cholesterol tended to be higher in ISNA patients compared with non-ISNA patients. OCT analysis revealed significantly thicker neointimal coverage as well as a lower number of uncovered struts in ISNA lesions compared with the other patients. LDL-cholesterol levels were correlated with the average neointima thickness (Spearman's rho = 0.46, P = 0.04). All the ISNA lesions were treated through initial thrombectomy followed by redo stenting in nine patients.
Our data show that ISNA is frequent in patients with VLST. These results suggest that OCT imaging is helpful in identifying the underlying mechanisms of VLST and, therefore, in the clinical decision-making process.
Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to the deposition of a genetic variant transthyretin essentially produced by the liver, and ...characterized by both sensorimotor and autonomic neuropathy. Liver transplantation (LT) is the most effective treatment to stop the progression of the disease. Cardiac amyloid infiltration is usually associated with cardiac denervation, restrictive cardiomyopathy, conduction disturbances, and sometimes sudden death. Whether the cardiac involvement related to amyloid deposition may be altered after LT remains unclear. We conducted the present study to define the outcome of cardiac involvement after LT in 31 patients with FAP (age, 39 +/- 12 yr). Patients were evaluated before and after LT (24 +/- 15 mo). Cardiac sympathetic denervation was assessed by both iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy and heart rate variability (HRV) analysis. The scintigraphic importance of sympathetic denervation was evaluated globally on planar imaging using heart-to-mediastinum activity ratio (H/M) measured 4 hours after injection, and regionally using single-photon emission tomography (SPET) imaging. Amyloid myocardial infiltration was assessed by echocardiography. Diffuse sympathetic denervation was found when using cardiac MIBG planar imaging in patients evaluated before LT and compared with 12 control subjects (H/M: 1.45 +/- 0.29 vs. 1.98 +/- 0.35, p < 0.001). On SPET images, defects were diffuse in 12 patients and focal in 19 patients, with predominance at the inferior and apical segments. No change in sympathetic innervation was found in patients after LT as assessed either with planar imaging (H/M after LT: 1.46 +/- 0.28, p = not significant vs. H/M before LT) or with SPET imaging. HRV nonspectral indexes showed that the standard deviation of all cycles was significantly lower in patients compared with control subjects, and remained unchanged after LT. Conduction disturbances and ventricular arrhythmias were associated with low cardiac MIBG uptake, and progressed after LT. The left ventricular wall was slightly thickened in patients, and a further increase was observed after LT (posterior wall from 9.2 +/- 1.8 to 10.1 +/- 2.3 mm, p = 0.02; septal wall from 10.6 +/- 2.7 to 12.1 +/- 4, p = 0.046). Neurologic status stabilized in 26 patients, but worsened in the 5 patients who had the most severe cardiac sympathetic denervation before LT as measured by MIBG imaging. The magnitude of the cardiac sympathetic denervation remained stable 2 years after LT in patients with FAP, whereas the cardiac amyloid infiltration progressed. The importance of cardiac sympathetic denervation found in FAP patients before LT was associated with a neurologic worsening after LT.
OBJECTIVES
The aim of this study was to assess the diagnosis of myocarditis in patients presenting with acute myocardial infarction (MI) and normal coronary angiograms.
BACKGROUND
Most often in these ...patients, the etiologic diagnosis remains unclear once they are found to have normal coronary arteries. The diagnosis of myocarditis mimicking MI is clinically relevant, because numerous arguments suggest a relation between myocarditis and dilated cardiomyopathy. Myocardial indium-111 (111In)-antimyosin antibody (AMA)/rest thallium-201 (201Tl) imaging allows noninvasive detection of myocarditis.
METHODS
Forty-five patients admitted to three intensive care units for suspicion of acute MI, with normal coronary angiograms, were investigated. Indium-111–AMA planar images and then a dual-isotope rest AMA/201Tl tomographic study were performed. Six-month echocardiographic follow-up was obtained in 80% of the patients with initial left ventricular (LV) wall motion abnormalities.
RESULTS
In eight patients, AMA and 201Tl scintigraphy were negative. In two patients, a matched 201Tl defect and focal AMA uptake suggested acute MI (due to prolonged vasospasm or spontaneously reperfused coronary occlusion). In 17 patients, diffuse AMA uptake over the whole LV suggested diffuse myocarditis. In 18 patients, focal AMA uptake with a normal 201Tl scan suggested diffuse but heterogeneous, or focal myocarditis. Complete functional recovery was observed in 81% of the patients with a pattern of myocarditis.
CONCLUSIONS
Among 45 patients presenting with acute MI and normal coronary angiograms, 38% had diffuse myocarditis and 40% had a scintigraphic pattern of heterogeneous or focal myocarditis. Short-term follow-up showed complete LV functional recovery in 81% of these patients.
A growing body of evidence suggests that the arrhythmogenic substrate underlying Brugada syndrome (BrS) is located in the right ventricular outflow tract (RVOT), and electrophysiological ...abnormalities recently evidenced most commonly concur in conduction slowing. Also, imaging studies reported wall motion abnormalities of the RVOT in patients with BrS, with a various extent of RV remodeling. However, there are no data regarding a potential relationship between electrophysiological alterations and contraction abnormalities in BrS.
We aimed to assess (1) the potential relationship between contraction delays of the RV quantified by phase analysis of equilibrium radionuclide angiography (ERNA), and the spontaneous ST-segment elevation pattern; and (2) to evidence RV remodeling in patients with BrS.
Seventy patients with BrS and 18 control subjects were included in the study. For the purpose of the study, the spontaneous ST-segment elevation pattern was graded simultaneously to ERNA acquisition. RV contraction delays and amplitude were assessed using multiharmonic phase analysis of ERNA, and ventricular volumes and ejection fraction were assessed using gated blood-pool single photon emission computed tomography.
RVOT contraction was delayed in patients with BrS, and RV contraction heterogeneity increased according to the pattern of ST-segment elevation, without impairment of the amplitude of contraction. RV volumes were greater in patients with BrS compared with control subjects, without impairment of the ejection fraction, whatever the ST-segment elevation pattern or the magnitude of contraction heterogeneity.
In patients with BrS, we found a relationship between RV contraction heterogeneity and ST-segment pattern, providing evidence of a functional modulation of the arrhythmogenic substrate.
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