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AIMS: Transthyretin cardiac amyloidosis (ATTR-CM) may be an underestimated cause of heart failure among geriatric patients and represent a unique phenotype and prognostic profile. METHODS AND RESULTS: This retrospective, observational, cohort study characterizes cardiac and extracardiac disorders at diagnosis and assesses prognosis among ATTR-CM patients based on age (geriatric vs. non-geriatric) and amyloidosis subtype (wild type, ATTRwt and hereditary, ATTRv). In total, 943 patients with ATTR-CM were included, of which 306 had ATTRv and 637 had ATTRwt. Among these, 331 (35.1%) were non-geriatric (<75 years), and 612 (64.9%) were geriatric (≥75 years). The population exhibited conduction abnormalities, atrial fibrillation and ischaemic heart disease that progressively deteriorated with age. Among ATTRwt patients, peripheral neuropathy, neurovegetative symptoms, and hearing loss were present across all age groups, but reports of carpal tunnel symptoms or surgery decreased with age. Conversely, among ATTRv patients, reports of extracardiac symptoms increased with age and Val122ILe mutation was highly prevalent among geriatric patients. The 3-year survival was higher among non-geriatric ATTR-CM patients (76%) than geriatric patients (55%) and predictors of 3-year mortality differed. Notably, predictors identified among geriatric patients were alkaline phosphatase (ALP) (HR = 1.004, 95% CI: [0.001-1.100)], troponin T hs (HR = 1.005, 95% CI: [1.001-1.120)] and tricuspid insufficiency (HR = 1.194, 95% CI: [1.02-1.230)]. Whereas, among non-geriatric patients, NT-proBNP (HR = 1.002, 95% CI: [1.02-1.04], global longitudinal strain (HR = 0.95, 95% CI: [0.922-0.989], and glomerular filtration rate (HR = 0.984, 95% CI: [0.968-1.00) were identified. We propose a 3-stage prognostic staging system combining troponin T hs (≥44 ng/L) and ALP levels (≥119 UI/L). In the geriatric population, this model discriminated survival more precisely than the National Amyloidosis Centre staging, particularly for classifying between stage 1 (82%), stage 2 (50%) and stage 3 (32%) for ATTRv and ATTRwt. CONCLUSIONS: These diagnostic and prognostic indicators, along with ATTR subtype, highlight the distinct characteristics of this important, geriatric ATTR-CM patient group. Recognizing these mortality markers can be valuable for geriatricians to improve the prognostic quality management of geriatric patients with ATTR-CM.
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BACKGROUND: Cardiac involvement in systemic light chain amyloidosis (AL) leads to chronic heart failure and is a major prognosis factor. Severe cellular defects are provoked in cardiac cells by tissue-deposited amyloid fibrils of misfolded free immunoglobulin light chains (LCs) and their prefibrillar oligomeric precursors. OBJECTIVE: Understanding the molecular mechanisms behind cardiac cell cytotoxicity is necessary to progress in therapy and to improve patient management. One key question is how extracellularly deposited molecules exert their toxic action inside cardiac cells. Here we searched for direct evidence of amyloid LC uptake by cardiomyocytes in patient biopsies. METHODS: We immunolocalized LCs in cardiac biopsies from four AL cardiac amyloidosis patients and analysed histopathological images by high resolution confocal microscopy and 3D image reconstruction. RESULTS: We show, for the first time directly in patient tissue, the presence of LCs inside cardiomyocytes, and report their proximity to nuclei and to caveolin-3-rich areas. Our observations point to macropinocytosis as a probable mechanism of LC uptake. CONCLUSIONS: Internalisation of LCs occurs in patient cardiomyocytes. This event could have important consequences for the pathogenesis of the cardiac disease by enabling interactions between amyloid molecules and cellular organelles inducing specific signalling pathways, and might bring new insight regarding treatment.
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BACKGROUND: Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. METHODS AND RESULTS: We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; P=0.19). CONCLUSIONS: Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
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Estenosis de la Válvula Aórtica , Cardiomiopatías , Sistema de Registros , Humanos , Masculino , Femenino , Prevalencia , Anciano , Estudios Retrospectivos , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Pronóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/mortalidad , Anciano de 80 o más Años , Neuropatías Amiloides Familiares/epidemiología , Neuropatías Amiloides Familiares/mortalidad , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/diagnóstico , Factores de Riesgo , Ecocardiografía , Persona de Mediana Edad , Amiloidosis/epidemiología , Amiloidosis/mortalidad , Amiloidosis/diagnóstico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/epidemiología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Prealbúmina/genética , Válvula Aórtica/diagnóstico por imagenRESUMEN
BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.
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Clopidogrel , Infarto del Miocardio , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Femenino , Masculino , Anciano , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Tiempo , Factores de Riesgo , Infarto del Miocardio/mortalidad , Enfermedad Crónica , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Necrosis , Medición de Riesgo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Stents , Hemorragia/inducido químicamenteRESUMEN
Introduction: Pulmonary vascular dysfunction during severe acute respiratory distress syndrome (ARDS) may lead to right ventricle (RV) dysfunction and acute cor pulmonale (ACP). The occurrence/persistence of ACP despite conventional extracorporeal membrane oxygenation (ECMO) is a challenging situation. We explored the usefulness of a specific dual-lumen cannula that bypasses the RV, and on which a veno-pulmonary arterial assist (V-P ECMO) was mounted, in ARDS patients. Methods: We report a case-series of ARDS patients put on conventional veno-arterial or veno-venous ECMO and presented refractory ACP as an indication for a reconfiguration to V-P ECMO using the ProtekDuo cannula. The primary endpoint was the mitigation of RV and pulmonary vascular dysfunction as assessed by the change in end-diastolic RV/left ventricle (LV) surface ratio. Results: Six patients had their conventional ECMO reconfigured to V-P ECMO to treat refractory ACP. There was a decrease in end-diastolic RV/LV surface ratio, as well as end-systolic LV eccentricity index, and lactatemia immediately after V-P ECMO initiation. The resolution of refractory ACP was immediately achieved in four of our six (66%) patients. The V-P ECMO was weaned after a median of 26 [8-93] days after implantation. All but one patient were discharged home. We detected one case of severe hemolysis with V-P ECMO and two suspected cases of right-sided infective endocarditis. Conclusion: V-P ECMO is useful to mitigate RV overload and to improve hemodynamics in case of refractory ACP despite conventional ECMO.
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BACKGROUND: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, pnon-inferiority<0·0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days. FUNDING: Meril Life Sciences.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Diseño de Prótesis , Índice de Severidad de la Enfermedad , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence. OBJECTIVES: The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures. METHODS: In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction. RESULTS: Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy. CONCLUSIONS: The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort.
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Ayuno , Satisfacción del Paciente , Humanos , Ayuno/sangre , Masculino , Femenino , Estudios Prospectivos , Método Simple Ciego , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Factores de Tiempo , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos , Angiografía Coronaria/efectos adversos , Hipoglucemia/inducido químicamente , Hipoglucemia/sangre , Síncope Vasovagal/etiología , Síncope Vasovagal/prevención & control , Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Medición de RiesgoRESUMEN
AIMS: Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. METHODS AND RESULTS: This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT ≤ 107 ng/L and NT-proBNP ≤ 3867 ng/L (n = 77; 33%); for stage 2 NT-proBNP > 3867 ng/L (n = 72; 30%). For stage 3, if troponin >107 ng/L, regardless of NT-proBNP then CB 4 µmol/L, was added (n = 41; 17.5%) and stage 4: CB > 4 µmol/L (n = 43; 18.5%). The median overall survival was 8 months 95% CI [2-24]. At 1 year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2 months (95% CI [11-18]) and stage 3, 6.6 months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n = 8 were MACS stage 3 and European stage IIIb 21.4% (n = 23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n = 29) were classified MACS stage 4 and 12.5% n = 9 were only MACS stage 2. CONCLUSIONS: The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.
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Cardiomiopatías , Humanos , Masculino , Femenino , Estudios Prospectivos , Pronóstico , Cardiomiopatías/sangre , Cardiomiopatías/mortalidad , Cardiomiopatías/diagnóstico , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Tasa de Supervivencia/tendencias , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Estudios de Seguimiento , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangreRESUMEN
OBJECTIVE: Left atrial appendage closure (LAAC) is recommended to decrease the stroke risk in patients with atrial fibrillation and contraindications to anticoagulation. However, age-stratified data are scarce. The aim of this study was to provide information on the safety and efficacy of LAAC, with emphasis on the oldest patients. METHODS: A nationwide, prospective, multicentre, observational registry was established by 53 French cardiology centres in 2018-2021. The composite primary endpoint included ischaemic stroke, systemic embolism, and unexplained or cardiovascular death. Separate analyses were done in the groups <80 years and ≥80 years. RESULTS: Among the 1053 patients included, median age was 79.7 (73.6-84.3) years; 512 patients (48.6%) were aged ≥80 years. Procedure-related serious adverse events were non-significantly more common in octogenarians (7.0% vs 4.4% in patients aged <80 years, respectively; p=0.07). Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events during the study was similar in both groups (3.0 vs 3.1/100 patient-years; p=0.85). By contrast, all-cause mortality was significantly higher in octogenarians (15.3 vs 10.1/100 patient-years, p<0.015), due to a higher rate of non-cardiovascular deaths (8.2 vs 4.9/100 patient-years, p=0.034). The rate of the primary endpoint was 8.1/100 patient-years overall with no statistically significant difference between age groups (9.4 and 7.0/100 patient-years; p=0.19). CONCLUSION: Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events after LAAC in this age group was similar to that in patients aged <80 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03434015).
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Apéndice Atrial , Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular , Tromboembolia , Anciano , Anciano de 80 o más Años , Humanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Cierre del Apéndice Auricular Izquierdo , Resultado del Tratamiento , Estudios Prospectivos , Isquemia Encefálica/complicaciones , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Tromboembolia/epidemiología , Tromboembolia/etiología , Tromboembolia/prevención & control , Apéndice Atrial/cirugía , Sistema de Registros , AnticoagulantesRESUMEN
The CARDIO-ARSIF registry has been continuously collecting comprehensive data on coronary angiography and percutaneous coronary interventions (PCI) performed in the 36 catheterization laboratories across the Île-de-France region since 2000. Over the period from 2003 to 2022, this registry has recorded information from more than 330,000 patients, encompassing more than one million procedures. Among these procedures, 58% consisted of coronary angiography, 13% were percutaneous coronary interventions (PCI), and the remaining 28% were PCI performed on an ad-hoc basis. This extensive dataset serves as a valuable resource for both qualitative and quantitative assessments of practices and the relevance of procedures in the field of coronary invasive cardiology. The results of these analyses undergo annual validation by a dedicated scientific committee and are shared with the teams of investigators. The exploitation of this data has led to scientific publications, with one notable finding being a consistent reduction in the radiation doses received by patients, regardless of the type of procedure.
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Cardiología , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Angiografía Coronaria/métodos , Sistema de Registros , Francia/epidemiologíaRESUMEN
BACKGROUND: Early cardiac amyloidosis (CA) diagnosis enables patients to access effective treatments for better long-term outcomes, yet it remains under-recognised, misdiagnosed and inadequately managed. AIM: To reduce diagnostic delays, we aimed to describe the epidemiological and clinical characteristics and changes over an 11-year period. METHODS: This was a retrospective, observational cohort study of all patients referred to the Henri-Mondor Hospital for suspected CA. RESULTS: Overall, 3194 patients were identified and 3022 were included and analysed. Our patients came from varied ethnic backgrounds, and more than half (55.2%) had confirmed CA. Over 11 years, referrals increased 4.4-fold, mostly from cardiologists. Notably, wild-type transthyretin amyloidosis (ATTRwt) became the predominant diagnosis, with referrals increasing 15-fold from 20 in 2010-2012 to 308 in 2019-2020. The number of amyloid light chain (AL) diagnoses increased, whilst variant transthyretin amyloidosis (ATTRv) numbers remained relatively stable. Concerning disease severity, AL patients presented more frequently with severe cardiac involvement whereas an increasing number of ATTRwt patients presented with National Amyloid Centre stage I (22.0% in 2013-2014 to 45.9% in 2019-2020). Lastly, among patients diagnosed with ATTRv in 2019-2020, 83.9% had ATTR Val122Ile cardiac phenotype. CONCLUSIONS: This study shows that increasing cardiologist awareness and referrals have increased CA diagnoses. With improved awareness and non-invasive diagnostic techniques, more patients with ATTRwt with milder disease and more ATTRv Val122Ile mutations are being referred and diagnosed. Although more AL cases are being recognised, patients are diagnosed with severe cardiac involvement.
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Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5 weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3 weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2 weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E'septal and E/E'lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF.
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Insuficiencia Cardíaca , Animales , Angiotensina II , Fibrosis , Hipertrofia Ventricular Izquierda , Volumen Sistólico , Porcinos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis. MATERIAL AND METHODS: This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis. RESULTS: Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, p < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, p < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, p = .018). CONCLUSION: This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.
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Neuropatías Amiloides Familiares , Prealbúmina , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Homocigoto , Heterocigoto , Estudios Retrospectivos , Prealbúmina/genética , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/complicacionesRESUMEN
BACKGROUND: The benefit related to the use of preprocedural computed tomography angiography (CCTA) on top of periprocedural echocardiography to plan percutaneous left atrial appendage closure (LAAC) procedures is still unclear. OBJECTIVES: The authors sought to evaluate the impact of preprocedural CCTA on LAAC procedural success. METHODS: In the investigator-initiated SWISS-APERO (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure) trial, patients undergoing echocardiography-guided LAAC were randomly assigned to receive the Amulet (Abbott) or Watchman 2.5/FLX (Boston Scientific) device across 8 European centers. According to the study protocol ongoing at the time of the procedure, the first operators had (CCTA unblinded group) or did not have (CCTA blinded group) access to preprocedural CCTA images. In this post hoc analysis, we compared blinded vs unblinded procedures in terms of procedural success defined as complete left atrial appendage occlusion as evaluated at the end of LAAC (short-term) or at the 45-day follow-up (long-term) without procedural-related complications. RESULTS: Among 219 LAACs preceded by CCTA, 92 (42.1%) and 127 (57.9%) were assigned to the CCTA unblinded and blinded group, respectively. After adjusting for confounders, operator unblinding to preprocedural CCTA remained associated with a higher rate of short-term procedural success (93.5% vs 81.1%; P = 0.009; adjusted OR: 2.76; 95% CI: 1.05-7.29; P = 0.040) and long-term procedural success (83.7% vs 72.4%; P = 0.050; adjusted OR: 2.12; 95% CI: 1.03-4.35; P = 0.041). CONCLUSIONS: In a prospective multicenter cohort of clinically indicated echocardiography-guided LAACs, unblinding of the first operators to preprocedural CCTA images was independently associated with a higher rate of both short- and long-term procedural success. Further studies are needed to better evaluate the impact of preprocedural CCTA on clinical outcomes.
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Apéndice Atrial , Humanos , Apéndice Atrial/diagnóstico por imagen , Estudios Prospectivos , Resultado del Tratamiento , Tomografía Computarizada por Rayos X , Angiografía por Tomografía ComputarizadaRESUMEN
BACKGROUND: Prospective data about transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) patients are limited. AIMS: We aimed to evaluate the clinical impact of the Evolut PRO and R (34 mm) self-expanding prostheses in BAV patients and explore the impact of different computed tomography (CT) sizing algorithms in a prospective registry. METHODS: A total of 149 bicuspid patients were treated in 14 countries. The primary endpoint was the intended valve performance at 30 days. Secondary endpoints were 30-day and 1-year mortality, severe patient-prosthesis mismatch (PPM) and the ellipticity index at 30 days. All study endpoints were adjudicated according to Valve Academic Research Consortium 3 criteria. RESULTS: The mean Society of Thoracic Surgeons score was 2.6% (1.7-4.2). Type I L-R BAV was observed in 72.5% of the patients. Evolut valve sizes 29 and 34 mm were utilised in 49.0% and 36.9% of the cases, respectively. The 30-day cardiac death rate was 2.6%; the 1-year cardiac death rate was 11.0%. Valve performance at 30 days was observed in 142/149 (95.3%) patients. The mean aortic valve area post-TAVI was 2.1 (1.8-2.6) cm2, and the mean aortic gradient was 7.2 (5.4-9.5) mmHg. No patient had more than moderate aortic regurgitation at 30 days. PPM was observed in 13/143 (9.1%) surviving patients and was severe in 2 patients (1.6%). Valve function was maintained at 1 year. The mean ellipticity index remained 1.3 (interquartile range 1.2-1.4). Overall, 30-day and 1-year clinical and echocardiography outcomes were similar between the two sizing strategies. CONCLUSIONS: BIVOLUTX demonstrated a favourable bioprosthetic valve performance and good clinical outcomes after TAVI with the Evolut platform in patients with bicuspid aortic stenosis. No impact from the sizing methodology could be identified.
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Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Enfermedades de las Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Estenosis de la Válvula Mitral , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Enfermedad de la Válvula Aórtica Bicúspide/etiología , Enfermedad de la Válvula Aórtica Bicúspide/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Constricción Patológica , Resultado del Tratamiento , Diseño de Prótesis , Estudios Prospectivos , Enfermedades de las Válvulas Cardíacas/cirugía , Estenosis de la Válvula Mitral/cirugía , Sistema de Registros , MuerteRESUMEN
BACKGROUND: Clinical outcomes and treatment selection after completing the randomized phase of modern trials, investigating antiplatelet therapy (APT) after percutaneous coronary intervention (PCI), are unknown. OBJECTIVES: The authors sought to investigate cumulative 15-month and 12-to-15-month outcomes after PCI during routine care in the MASTER DAPT trial. METHODS: The MASTER DAPT trial randomized 4,579 high bleeding risk patients to abbreviated (n = 2,295) or standard (n = 2,284) APT regimens. Coprimary outcomes were net adverse clinical outcomes (NACE) (all-cause death, myocardial infarction, stroke, and BARC 3 or 5 bleeding); major adverse cardiac and cerebral events (MACCE) (all-cause death, myocardial infarction, and stroke); and BARC type 2, 3, or 5 bleeding. RESULTS: At 15 months, prior allocation to a standard APT regimen was associated with greater use of intensified APT; NACE and MACCE did not differ between abbreviated vs standard APT (HR: 0.92 [95% CI: 0.76-1.12]; P = 0.399 and HR: 0.94 [95% CI: 0.76-1.17]; P = 0.579; respectively), as during the routine care period (HR: 0.81 [95% CI: 0.50-1.30]; P = 0.387 and HR: 0.74 [95% CI: 0.43-1.26]; P = 0.268; respectively). BARC 2, 3, or 5 was lower with abbreviated APT at 15 months (HR: 0.68 [95% CI: 0.56-0.83]; P = 0.0001) and did not differ during the routine care period. The treatment effects during routine care were consistent with those observed within 12 months after PCI. CONCLUSIONS: At 15 months, NACE and MACCE did not differ in the 2 study groups, whereas the risk of major or clinically relevant nonmajor bleeding remained lower with abbreviated compared with standard APT. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).
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Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Quimioterapia Combinada , Stents Liberadores de Fármacos/efectos adversos , Hemorragia/inducido químicamente , Infarto del Miocardio/complicaciones , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
Background and aims: Self-reported questionnaires are useful for estimating the health-related quality of life (HR-QoL), impact of interventions, and prognosis. To our knowledge, no HR-QoL questionnaire has been developed for cardiac amyloidosis (CA). This study aimed to validate Amylo-AFFECT-QOL questionnaire to assess HR-QoL and its prognostic value in CA. Methods: A self-reported questionnaire, "Amylo-AFFECT" had been designed and validated for CA symptoms evaluation and screening by physicians. It was adapted here to assess HR-QoL (Amylo-AFFECT-QOL) and its prognostic value in CA. To validate the theoretical model, internal consistency and convergent validity were assessed, particularly correlations between Amylo-AFFECT-QOL and the HR-QoL Minnesota Living Heart Failure (MLHF) questionnaire. Results: Amylo-AFFECT-QOL was completed by 515 patients, 425 of whom (82.5%) had CA. Wild-type and hereditary transthyretin amyloidosis (ATTRwt and ATTRv) and immunoglobulin light-chain amyloidosis (AL) were diagnosed in 47.8, 14.7, and 18.8% of cases, respectively. The best HR-QoL evaluation was obtained with five dimensions: "Heart failure," "Vascular dysautonomia," "Neuropathy," "Ear, gastrointestinal, and urinary dysautonomia," and "Skin or mucosal involvement." The global Amylo-AFFECT-QOL and MLHF scores showed significant positive correlations (rs = 0.72, p < 0.05). Patients with a final diagnosis of CA had a global Amylo-AFFECT-QOL score significantly higher than the control group composed by patients with other diagnoses (22.2 ± 13.6 vs. 16.2 ± 13.8, respectively, p-value < 0.01). According to the Amylo-AFFECT-QOL global results, ATTRv patients' QoL was more affected than AL patients' QoL or ATTRwt patients' QoL. Patients with a higher HR-QoL score had a greater risk of death or heart transplant after 1 year of follow-up (log-rank < 0.01). Conclusion: Amylo-AFFECT-QOL demonstrates good psychometric properties and is useful for quantifying HR-QoL and estimating CA prognosis. Its use may help to improve overall management of patients with CA.
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OBJECTIVE: To evaluate the real-life use of a modified Gillmore algorithm with a "one-stop-shop" approach, bone scintigraphy (BS), a monoclonal gammopathy test (GT), a salivary gland biopsy (SGB), and genetic testing performed at the same time for the diagnosis of cardiac amyloidosis at the French National Reference Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil, France). METHODS: This retrospective cohort study included a total of 1222 patients with suspected amyloidosis who underwent BS and GT between June 2008 and May 2019. RESULTS: Of 1222 patients, 349 had no cardiac uptake on BS and negative GT (BS-/GT-), 276 were BS-/GT positive (GT+), 420 patients were BS+/GT-, and 177 were BS+/GT+. Our one-stop-shop check-up enabled us to diagnose 892 (72.9%) patients; 330 (27.0%) patients required additional examinations, such as mass spectrometry and/or a cardiac biopsy. This subset notably included 112 patients with amyloid light chain amyloidosis. More than 64% of the patients with transthyretin amyloidosis or another type of amyloidosis were diagnosed during the one-stop shop visit. Sensitivity and specificity of BS for transthyretin amyloidosis diagnosis was 99% and 96%, respectively. For amyloid light chain diagnosis, sensitivity and specificity were 100% and 76%, respectively, for GT and 54% and 100%, respectively, for SGB. Of 910 transthyretin genetic tests, 205 (17%) detected mutations. CONCLUSION: The results of our real-life cohort study confirmed the ability of a one-stop-shop approach with a modified Gillmore algorithm to diagnose cardiac amyloidosis and the interest of simultaneous testing for earlier diagnosis. The SGB has diagnostic value because it is easy, quick, and less invasive than a cardiac biopsy.