Restrictive cardiomyopathy: definition and diagnosis

Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy

Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta-analysis of screening studies

Aims An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data. Methods and results We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non-cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%-1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%-20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%-15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%-4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%-10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%-9%); severe aortic stenosis (n = 7), 8% (95% CI 5%-13%); autopsy series of 'unselected' elderly individuals (n = 4), 21% (95% CI 7%-39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR-CA, but the average percentage of patients with amyloid light-chain (AL) CA was up to 18%. Conclusions Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR-CA accounts for many cases of CA across the different settings, but AL-CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women

Ultrasound lung comets for serial assessment of pulmonary congestion in heart failure

Background: Serial chest radiographs are too insensitive and therefore NOT recommended for monitoring pulmonary congestion in heart failure patients (AHA/ACC guidelines 2006). Ultrasound lung comets (ULCs) are a simple, quantitative chest sonography sign of pulmonary congestion, originating from water-thickened interlobular septa, and might represent a convenient alternative to chest x-ray in this clinical setting. Aim: To assess whether dynamic changes in ULCs could mirror variations in clinical status and natriuretic peptides. Methods: 104 patients (28 females; age 70?11 years) admitted with dyspnoea (NYHA class &#8805;II) to a Cardiology or Emergency Department were evaluated. NT-proBNP assessment and ULC were independently performed at admission and again before discharge. A patient ULC score was obtained by summing the number of comets from each of the scanning spaces from second to fifth intercostal spaces on anterior chest. Patients were considered "responders" to therapy when NYHA class decreased &#8805;1 grade at discharge. Results: Responders (group I, n=90) and non-responders (group II, n=14) had similar NT-proBNP (I=5560?6643 vs II=5470?4047 ng/l, p=.313), and ULCs number (I=27?34 vs II=34?24, p=.133) at admission. At discharge, responders had lower NT-proBNP (I=3633?5194 vs II=4654?3366 ng/l, p<.05) and ULCs (I=11?12 vs II=28?32, p<.01, see figure) when compared to non-responders. Variation in NT-proBNP somewhat mirrored variations in ULCs (r=.322, p<0.0001). Conclusions: ULC variations mirror changes in clinical functional class and natriuretic peptides in patients hospitalized with acute dyspnoea. ULCs represent an objective parameter of clinical improvement, useful for serial assessment of extra-vascular lung water in patients admitted with acute dyspnoea

Fotografías del terremoto del Cuzco de 1950 - Archivo Luis E. Valcárcel

Este álbum contiene una selección de fotografías de los daños ocasionados por el terremoto de 1950 en el Cusco, donde se puede observar el estado en que quedó la ciudad, especialmente en las antiguas casonas e iglesias de aquel tiempo. Estas fotografías pertenecieron al Dr. Luis E. Valcárcel y en la actualidad el propietario es su nieto, el Sr. Luis Fernando Brugué Valcárcel. Esta valiosa colección fotográfica, escaneada por el Centro Nacional de Información Cultural, ha sido incorporada a la Biblioteca Virtual del Ministerio de Cultura, gracias al apoyo de Rosalyn Aranda Díaz, Directora de la Oficina de Comunicaciones e Imagen Institucional, Diego Viaña Rosa-Pérez, Percy Ramírez Medina y Leonardo Carlos Napán. Este valioso álbum contiene 70 fotografías

Arqueología de la Región Lima - Fotografías del Archivo Luis E. Valcárcel

Colección de fotografías de los sitios arqueológicos de Cajamarquilla, Chipprac, huacas de la hacienda Márquez, Pachacamac y Paramonga, que pertenecieron al ilustre peruanista el Dr. Luis E. Valcárcel y que en la actualidad son propiedad de su nieto, el Sr. Luis Fernando Brugué Valcárcel. Esta valiosa colección fotográfica, escaneada por el Centro Nacional de Información Cultural, ha sido incorporada a la Biblioteca Virtual del Ministerio de Cultura, gracias al apoyo de don Claudio Félix Poma Hermoza, jefe de la Oficina de Comunicación e Imagen Institucional (OCII), del Ministerio de Cultura. La edición digital fue realizada por don Leonardo Carlos Napán, experto diseñador gráfico de dicha Oficina

Expansion of the National Amyloidosis Centre staging system to detect early mortality in transthyretin cardiac amyloidosis

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is stratified into prognostic categories using the National Amyloidosis Centre (NAC) staging system. The aims of this study were to further expand the existing NAC staging system to incorporate an additional disease stage that would identify patients at high risk of early mortality. Methods and results: The traditional NAC staging system (stage 1: N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≤3000 ng/L and estimated glomerular filtration rate [eGFR] ≥45 ml/min; stage 3: NT-proBNP &gt;3000 ng/L and eGFR &lt;45 ml/min; stage 2: remainder) was expanded by the introduction of a new stage 4 (defined as NT-proBNP ≥10 000 ng/L irrespective of eGFR) and studied in 2042 patients. The optimal NT-proBNP cut-point was established using time-dependent receiver operating characteristic curves in the subgroup of patients with NAC stage 3 disease. Mortality at 1 year according to NAC stage was 2.3% (n = 20/886) for stage 1, 8.8% (n = 62/706) for stage 2, 10.4% (n = 28/270) for stage 3, and 30.6% (n = 55/180) for stage 4 (log-rank p &lt; 0.001). After adjustment for age, mortality hazard for stage 4 was &gt;15-fold higher than that of stage 1 (hazard ratio [HR] 15.5; 95% confidence interval [CI] 9.3-26.1) and &gt;3-fold higher than that of stage 3 (HR 3.4; 95% CI 2.2-5.4). The increased risk of early mortality was consistent across the different genotypes and subclasses of patients based on the severity of heart failure symptoms and echocardiographic parameters. Conclusions: The proposed modification of the NAC staging system identifies patients with ATTR-CA at a high risk of early mortality, who may benefit from a more intensive treatment strategy, and who are most likely to experience an event early in the course of a clinical trial

Left ventricular wall thickness and severity of cardiac disease in women and men with transthyretin amyloidosis

Aims: Cardiac amyloidosis (CA) is due to a deposition of amyloid fibrils in the heart causing an increase in wall thickness. A left ventricular (LV) wall thickness ≥12 mm plus at least one red flag should raise the suspicion of CA. As normal values of LV wall thickness are lower in women, the adoption or the same cut-off values for men and women could lead to underdiagnosis or delayed diagnosis in women. We investigated the relationship between LV wall thickness and the severity of cardiac involvement in women and men with transthyretin (ATTR) CA. Methods and results: We evaluated 330 consecutive patients diagnosed with ATTR-CA at three centres (Pisa, n = 232; Brescia, n = 69; Trieste, n = 29). Interventricular septum (IVS) and posterior wall (PW) thickness values were lower in women (n = 53, 16%) than men, but most differences were abolished when indexing by body surface area (BSA), height, or height, suggesting similar disease severity when accounting for the smaller body size of women. PW thickness indexed for height was even higher in women. We also searched for correlations between IVS and PW thickness and other indicators of the severity of cardiac disease. IVS values indexed by height displayed tighter associations with N-terminal pro-B-type natriuretic peptide values than non-indexed IVS values. Similarly, indexed values displayed closer relationships with relative wall thickness, E/e' ratio, and tricuspid annular plane systolic excursion. Conclusions: Indexed LV wall thickness values, particularly by height, reflect more accurately the severity of cardiac involvement than non-indexed values

Atrial electro-functional predictors of incident atrial fibrillation in cardiac amyloidosis

Background: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. Objective: to investigate the atrial electro-functional predictors of incident AF in CA. Methods: A multicenter, observational study performed in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiogram (ECG) and cardiac magnetic resonance (CMR). The primary endpoint was new-onset AF occurrence. Results: Overall, 96 patients (AL-CA: n=40; ATTR-CA n=56) were enrolled. During an 18-month median follow-up (Q1-Q3:7-29), 30 patients (29%) had incident AF. Compared with those without, patients with AF were older (79 vs 73 years, p=0.001) and more frequently with ATTR (73% vs 27%, p78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by one (8.5%) or none (7.6%) of these three risk factors. Conclusions: In patients with CA, older age, IAB on 12-lead ECG and reduced LAEF on CMR are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features

Prevalence and clinical outcomes of isolated or combined moderate to severe mitral and tricuspid regurgitation in patients with cardiac amyloidosis

Aims: Evidence on the epidemiology and prognostic significance of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with cardiac amyloidosis (CA) is scarce. Methods and results: Overall, 538 patients with either transthyretin (ATTR, n = 359) or immunoglobulin light-chain (AL, n = 179) CA were included at three Italian referral centres. Patients were stratified according to isolated or combined moderate/severe MR and TR. Overall, 240 patients (44.6%) had no significant MR/TR, 112 (20.8%) isolated MR, 66 (12.3%) isolated TR, and 120 (22.3%) combined MR/TR. The most common aetiologies were atrial functional MR, followed by primary infiltrative MR, and secondary TR due to right ventricular (RV) overload followed by atrial functional TR. Patients with isolated or combined MR/TR had a more frequent history of heart failure (HF) hospitalization and atrial fibrillation, worse symptoms, and higher levels of NT-proBNP as compared to those without MR/TR. They also presented more severe atrial enlargement, atrial peak longitudinal strain impairment, left ventricular (LV) and RV systolic dysfunction, and higher pulmonary artery systolic pressures. TR carried the most advanced features. After adjustment for age, sex, CA subtypes, laboratory, and echocardiographic markers of CA severity, isolated TR and combined MR/TR were independently associated with an increased risk of all-cause death or worsening HF events, compared to no significant MR/TR [adjusted HR 2.75 (1.78-4.24) and 2.31 (1.44-3.70), respectively]. Conclusion: In a large cohort of patients with CA, MR, and TR were common. Isolated TR and combined MR/TR were associated with worse prognosis regardless of CA aetiology, LV, and RV function, with TR carrying the highest risk

Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression. Objectives: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA. Methods: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n&nbsp;=&nbsp;1,598) and validated in the external cohort from the remaining centers (n&nbsp;=&nbsp;677). Results: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase &gt;700&nbsp;ng/L and &gt;30%), which was associated with mortality (NAC cohort: HR: 1.82; 95%&nbsp;CI: 1.57-2.10; P&nbsp;&lt; 0.001; validation cohort: HR: 1.75; 95%&nbsp;CI: 1.32-2.33; P&nbsp;&lt; 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95%&nbsp;CI: 1.62-2.18; P&nbsp;&lt; 0.001; validation cohort: HR: 2.05; 95%&nbsp;CI: 1.53-2.74; P&nbsp;&lt; 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95%&nbsp;CI: 1.65-2.27; P&nbsp;&lt; 0.001; validation cohort: HR: 1.94; 95%&nbsp;CI: 1.36-2.77; P&nbsp;&lt; 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95%&nbsp;CI: 2.42-3.67; P&nbsp;&lt; 0.001; validation cohort: HR: 3.23; 95%&nbsp;CI: 2.17-4.79; P&nbsp;&lt; 0.001). Conclusions: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of&nbsp;mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA