Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

BACKGROUND: The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. METHODS AND RESULTS: We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. CONCLUSIONS: Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison

Aims: Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results: We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion: In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed

Troponin in non-ischaemic dilated cardiomyopathy

Non-ischaemic dilated cardiomyopathy (DCM) is a disease characterised by progressive left ventricular remodelling and dysfunction. DCM represents a major cause of morbidity and mortality. Cardiac troponins are sensitive biohumoral markers of myocyte injury that are used for diagnostic purposes in acute coronary syndromes but that are also detected in DCM. Several pathophysiological factors (wall stress, neurohormonal activation, inflammation, metabolic dysfunction, microvascular ischaemia) have been advocated to explain subtle ongoing necrosis in DCM. In particular, new ultrasensitive assays expand the detection range toward physiological cardiac troponin levels, allowing accurate biohumoral characterisation of myocardial remodelling from the early stages of DCM. Moreover, several clinical studies have demonstrated that increased cardiac troponin plasma levels are associated with worse prognosis and that further increases in cardiac troponin over time contribute to additional risk. Serial plasma cardiac troponin evaluation represents an accurate marker of disease evolution and risk stratification in DCM, identifying high-risk patients who need strict follow-up and enhanced therapeutic effort. © TOUCH BRIEFINGS 2011

Markers of arrhythmogenic risk in hypertensive subjects.

Hypertension is increasingly considered a strong and independent risk factor for supraventricular and ventricular arrhythmias. The presence and complexity of both supraventricular and ventricular arrhythmias influence morbidity, mortality, as well as the quality of life of patients. Diastolic dysfunction of the left ventricle, left atrial size and function, and left ventricular hypertrophy have been suggested as the foremost underlying risk factors for supraventricular and ventricular arrhythmias in hypertensive patients. In particular, the presence of hypertension is a risk for sudden death and this risk is higher in those with left ventricular hypertrophy. Moreover, arrhythmias in the hypertrophic heart are often facilitated and aggravated by electrolyte disturbances, sympatho-vagal unbalance, transient blood pressure peaks, and occurrence of myocardial ischaemia. Several noninvasive biohumoral, electrocardiographic and imaging parameters have been widely investigated to identify hypertensive patients at higher risk for the development of arrhythmias. These parameters include neurohormones, signal averaged analysis of P wave, QT interval dispersion, heart rate variability, ventricular late potentials and T wave morphology analysis, as well as echocardiographic and magnetic resonance indexes of atrial and ventricular shape and function. The aim of this review is to evaluate the relationship of high blood pressure with ventricular and supraventricular arrhythmias, to discuss the available biomarkers for arrhythmic risk assessment in hypertensive patients and the effects of a tailored tight blood pressure control on the occurrence of arrhythmia