June 2019 at a Glance: From Genetics to Haemodynamics, Biomarkers and Imaging for the Prediction of Outcomes

Genetic status affects the clinical course of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Hermida et al.1 compared the outcomes of desmoglein-2 (DSG2) mutation carriers to those with plakophilin-2 (PKP2) mutation. There were no differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave and more left ventricular (LV) dysfunction at diagnosis. During a median follow-up of 5.6 years, DSG2 and PKP2 mutation carriers had a similar risk of sustained ventricular arrhythmia, but DSG2 mutation carriers were at higher risk of transplantation/heart failure (HF)-related death. Thus, DSG2 mutation is associated with a high risk of end-stage HF, compared to PKP2 mutation, and careful haemodynamic monitoring is needed in these patients.1 The Fontan operation is associated with significant long-term morbidity and mortality. Miranda et al.2 divided 84 adult Fontan patients into four different haemodynamic profiles based on Fontan pressures and cardiac index. The normal cardiac index/high Fontan pressure haemodynamic profile was an independent predictor of mortality. A position statement by the Heart Failure Association (HFA) gives a thorough update of the role of natriuretic peptides, brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and mid-regional pro-atrial natriuretic peptide, in the diagnosis and prognostic assessment of patients with HF. This comprehensive article summarises all the most recent data and is a reference for clinical practice and future research.3 An analysis of 2179 patients enrolled in A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) and 1703 patients in a validation cohort showed that higher plasma bio-adrenomedullin levels have a strong correlation with markers of congestion and were independently associated with an increased risk of all-cause mortality and HF hospitalization.4 Multi-organ dysfunction, assessed using markers of myocardial injury and of kidney and liver dysfunction, in patients hospitalized for acute HF was a strong predictor of outcomes with a linear relationship between the number of organs showing dysfunction and risk of death.5 This study confirms and extends previous data and hypotheses.6, 7 Lung ultrasound plays a major role in the assessment of patients with acute and chronic HF.8, 9 Pivetta et al.10 tested its usefulness for the diagnosis of HF in 518 patients with breathlessness in the emergency department in a prospective, randomized, study. The addition of lung ultrasound increased the diagnostic accuracy compared with the simple clinical assessment whereas a standard approach with the use of chest X-ray and NT-proBNP plasma levels did not reach statistical significance compared with clinical assessment alone. Combining lung ultrasound with clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to only 2.42 cases/100 patients in the chest X-ray/NT-proBNP group. This study shows the greater accuracy of lung ultrasound compared with the standard approach for the diagnosis of HF in the emergency department.10 Recent data show that many patients with Takotsubo syndrome may have poor outcomes with an event rate comparable to that of patients after acute myocardial infarction.11, 12 Heart rate and systolic blood pressure are major prognostic variables.13 Citro et al.14 analysed the value of LV ejection fraction (LVEF) measured at baseline as prognostic marker in these patients. Patients with a LVEF ≤35% at the time of admission were older and were more likely to develop acute HF, cardiogenic shock and need for intra-aortic balloon pump support. LVEF on admission and age were independent predictors of an increased rate of major adverse cardiac events during follow-up. Risk scores still have a major role in the clinical assessment and prognostic stratification of HF patients.15 O'Connor et al.16 analysed 35 baseline clinical variables from the 894 high-risk HF patients enrolled in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial with the aim to develop a prognostic score. Models were developed for the prediction of the primary composite endpoint of cardiovascular death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. The most important predictor in all these models was NT-proBNP. Hispanic ethnicity, low sodium and high heart rate were selected in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score.16