Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

Potential clinical relevance of cardiac magnetic resonance to diagnose cardiac light chain amyloidosis

Background While patients with cardiac transthyretin amyloidosis are easily diagnosed with bone scintigraphy, the detection of cardiac light chain (AL) amyloidosis is challenging. Cardiac magnetic resonance (CMR) analyses play an essential role in the differential diagnosis of cardiomyopathies; however, limited data are available from cardiac AL-Amyloidosis. Hence, the purpose of the present study was to analyze the potential role of CMR in the detection of cardiac AL-amyloidosis. Methods We included 35 patients with proved cardiac AL-amyloidosis and two control groups constituted by 330 patients with hypertrophic cardiomyopathy (HCM) and 70 patients with arterial hypertension (HT), who underwent CMR examination. The phenotype and degree of left ventricular (LV) hypertrophy and the amount and pattern of late gadolinium enhancement (LGE) were evaluated. In addition, global and regional LV strain parameters were also analyzed using feature-tracking techniques. Sensitivity and specificity of several CMR parameters were analyzed in diagnosing cardiac AL-amyloidosis. Results The sensitivity and specificity of diffuse septal subendocardial LGE in diagnosing cardiac AL-amyloidosis was 88% and 100%, respectively. Likewise, the sensitivity and specificity of septal myocardial nulling prior to blood pool was 71% and 100%, respectively. In addition, a LV end-diastolic septal wall thickness ≥ 15 mm had an optimal diagnostic performance to differentiate cardiac AL-amyloidosis from HT (sensitivity 91%, specificity 89%). On the other hand, a reduced global LV longitudinal strain (&lt; 15%) plus apical sparing (apex-to-base longitudinal strain &gt; 2) had a very low sensitivity (6%) in detecting AL-Amyloidosis, but with very high specificity (100%). Conclusions The findings from this study suggest that CMR could have an optimal diagnostic performance in the diagnosis of cardiac AL-amyloidosis. Hence, further larger studies are warranted to validate the findings from this study. </jats:sec

Practical Management of Cardiovascular Adverse Events with BTKi Treatment in Patients with Chronic Lymphocytic Leukemia : A Consensus Report by Hematologists and Cardiologists

Cardiovascular (CV) adverse events (AEs), especially atrial fibrillation (AF) and hypertension, have been reported in patients receiving treatments for chronic lymphocytic leukemia (CLL), including Bruton's tyrosine kinase inhibitors (BTKis). Although these AEs are managed effectively in most cases and AE management guidelines exist, practical management approaches are inconsistent across regions and practices. We aimed to address these inconsistencies by developing consensus recommendations.A European expert panel was assembled comprising eight hematologists and six cardiologists. Literature analysis, expert interviews, and the Delphi method were used to gain consensus on screening, monitoring, and treatment of AF and hypertension statements.Maintaining BTKi treatment is paramount to maximize time to next treatment; for patients at high risk of progression, this can be achieved by appropriately treating hypertension and AF and adjusting the BTKi dose. Patients should be risk-stratified as low, moderate, high, or very high risk of cancer therapy-related CV toxicity and treated according to their disease status so that CLL treatment can be maintained. Patient education on symptom monitoring, home blood pressure monitoring, and electrocardiograms (baseline, every 3 months) are recommended to detect/monitor AF and hypertension. Close collaboration between hematologists and cardiologists is vital to achieve optimal patient outcomes

Reproducibility of stain analyses.

Intraclass correlation analysis for interobserver variability in strain parameters. (DOCX)</p

Diagnostic accuracy of CMR parameters in differentiating cardiac AL-amyloidosis from HCM and cardiac AL-amyloidosis from controls with HT.

Results of the ROC curve analyses. (DOCX)</p

Fig 3 -

Representative late gadolinium enhancement images of patients with hypertrophic cardiomyopathy (A), cardiac AL-amyloidosis (B, C) and arterial hypertension (D) in a short-axis slice. A) Patchy mid-myocardial LGE in the hypertrophic segments typical for HCM (no diffuse subendocardial LGE, normal contrast kinetics). Myocardial nulling prior to blood pool nulling (B), and diffuse subendocardial LGE (C) typical for CA. D) Concentric hypertrophy without diffuse subendocardial LGE and with normal contrast kinetics in a patient with arterial hypertension.</p

Table 2 - Potential clinical relevance of cardiac magnetic resonance to diagnose cardiac light chain amyloidosis

Table 2 - Potential clinical relevance of cardiac magnetic resonance to diagnose cardiac light chain amyloidosis</p

Study flow chart.

Study flow chart.</p

Study’s minimal data set.

(XLSX)</p

Demographic and CMR characteristics of the study population.

Demographic and CMR characteristics of the study population.</p