Editorial Board

Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/mL (IQR 30.5–194.9), NT-proBNP 337.9 pg/mL (IQR 73.0–2584.0), troponin T 0.03 μg/L (IQR 0.01–0.05), and troponin I 0.08 μg/L (IQR 0.04–0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Three-year overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1–Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR. Conclusions: In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR

Cardiac resynchronization therapy: a comparison among left ventricular bipolar, quadripolar and active fixation leads

We evaluated the performance of 3 different left ventricular leads (LV) for resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n = 136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8 [email protected] ms, safety margin between myocardial and phrenic threshold <2V, LV dislodgement and failure to achieve the target pacing site), (b) composite clinical endpoint (CE) (death, hospitalization for heart failure, heart transplantation, lead extraction for infection), (c) reverse remodeling (RR) (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL, AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64% and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant differences in CE (p = 0.380). On a multivariable analysis, “non-BL leads” was the single predictor of an improved clinical outcome. QL and AFL are superior to conventional BL by enhancing pacing of the target site: AFL through prevention of lead dislodgement while QL through improved management of phrenic nerve stimulation

Real-world versus trial patients with transthyretin amyloid cardiomyopathy

Transthyretin (TTR) amyloid cardiomyopathy (ATTR‐AC) is caused either by single‐point mutations in the TTR gene (ATTRv‐AC) or by deposition of the wild‐type protein (ATTRwt‐AC).1 Long been considered a rare disease, ATTR‐AC has been increasingly recognized in recent years, particularly among the elderly,1 mostly due to the possibility of a non‐invasive diagnosis through bone scintigraph

Multi-imaging investigation to evaluate the relationship between serum cystatin c and features of atherosclerosis in Non-ST-Segment elevation acute coronary syndrome

Objectives: High cystatin C(CysC) levels are associated with impaired cardiovascular outcome. Whether CysC levels are independently related to the atherosclerosis burden is still controversial. Methods: We enrolled 31 non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. Patients were divided into 2 groups on the basis of median value of serum CysC. Using the high CysC group as a dependent variable, univariable and multivariable analyses were used to evaluate the association between CysC and three different features of atherosclerosis: 1) coronary plaque vulnerability as assessed by optical coherence tomography (OCT), 2) coronary artery calcium (CAC) by means of computed tomography scan, and 3) aortic wall metabolic activity, as assessed using 18 F-Fluorodeoxyglucose-positron emission tomography ( 18 F-FDG-PET). Results: After univariable and multivariable analyses, 18 F-FDG uptake in the descending aorta (DA) was independently associated with a low level of CysC [(Odds Ratio = 0.02; 95%CI 0.0004-0.89; p = 0.044; 18 F-FDG uptake measured as averaged maximum target to blood ratio); (Odds Ratio = 0.89; 95%CI 0.82-0.98, p = 0.025; 18 F-FDG uptake measured as number of active slices)]. No trend was found for the association between CysC and characteristics of OCT-assessed coronary plaque vulnerability or CAC score. Conclusions: In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), 18 F-FDG uptake in the DA was associated with a low level of serum CysC. There was no relation between CysC levels and OCT-assessed coronary plaque vulnerability or CAC score. These findings suggest that high levels of CysC may not be considered as independent markers of atherosclerosis

Exercise stress echocardiography is superior to rest echocardiography in predicting left ventricular reverse remodelling and functional improvement after cardiac resynchronization therapy

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Grey zones in the supportive treatments of cardiac amyloidosis

Recent advances in the diagnosis and treatment of cardiac amyloidosis (CA) have translated into a longer life expectancy of patients and more challenging clinical scenarios. Compared to the past, patients with CA and heart failure (HF) currently encountered in clinical practice are a more heterogeneous population and require tailored strategies. The perception of CA as a treatable disease has opened new possibilities for the management of these patients, but many grey areas remain to be explored. The aim of this review is to provide practical suggestions for daily clinical activity in the management of challenging scenarios in CA, including the effectiveness and tolerability of evidence-based HF medication; rate vs. rhythm control in atrial fibrillation, thromboembolic risk, and anticoagulation therapies; replacement of severe aortic valve stenosis; the impact of implantable cardioverter defibrillator on survival; and the usefulness of cardiac resynchronization therapy

Nuclear imaging for cardiac amyloidosis

Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis, but has its limitations. Accordingly, there is a need for non-invasive modalities to diagnose cardiac amyloidosis. Echocardiography and ultrasound and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Nuclear medicine has gained a precise role in this context: several imaging modalities have become available for the diagnosis and prognostic stratification of cardiac amyloidosis during the last two decades. The different classes of radiopharmaceuticals have the potential to bind different constituents of the amyloidotic infiltrates, with some relevant differences among the various aetiologic types of amyloidosis and the different organs and tissues involved. This review focuses on the background of the commonly used modalities, their present clinical applications, and future clinical perspectives in imaging patients with (suspected) cardiac amyloidosis. The main focus is on conventional nuclear medicine (bone scintigraphy, cardiac sympathetic innervation) and positron emission tomography

A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD)

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The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy.

The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype-phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves