July 2019 at a Glance: Imaging of Congestion, Sodium–Glucose Co-Transporter 2 Inhibitors, Myocardial Function and Mitraclip Trials

Peripartum cardiomyopathy is generally defined as heart failure (HF) with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the months following delivery in women without another known cause of HF. Its outcome ranges from full recovery to persistent left ventricular (LV) dysfunction or even death.1, 2 An updated position statement of the Heart Failure Association (HFA) summarizes the pathophysiology, diagnosis and current management of this important condition.3 Sodium–glucose co-transporter 2 (SGLT2) inhibitors reduce HF-related events in patients with type 2 diabetes at high cardiovascular risk.4, 5 Ongoing randomized controlled trials are evaluating their efficacy in non-diabetic patients with HF. Insights regarding their potential role and mechanisms of action come from experimental studies. Yurista et al.6 assessed the effects of SGLT2 inhibition with empagliflozin in non-diabetic rats with post-myocardial infarction LV dysfunction induced by coronary artery ligation. In addition to a two-fold increase in diuresis without adverse effects on renal function, empagliflozin treatment increased LV ejection fraction, attenuated cardiomyocyte hypertrophy, interstitial fibrosis, myocardial oxidative stress and mitochondrial DNA damage with normalization of myocardial uptake and oxidation of glucose and fatty acids, and increased ATP production. Circulating ketone levels and myocardial expression of the ketone body transporter and of two critical ketogenic enzymes were also increased consistent with an increase in their myocardial utilization. Thus, in addition to diuresis, SGLT2 inhibition can favourably affect myocardial metabolism. Trimethylamine N-oxide (TMAO) is a circulating molecule derived from gut microbiome-mediated processing of carnitine and/or choline (e.g. red meat and egg yolk as dietary sources). In this analysis of the systems BIOlogy Study to TAilored Treatment in Chronic HF (BIOSTAT-CHF) cohort, Suzuki et al.7 confirmed that high TMAO plasma levels are independent predictors of mortality and of the composite outcome of death and HF hospitalizations. However, differently from B-type natriuretic peptide (BNP) levels, TMAO levels did not change after medical treatment, consistent with its lack of influence on gut microbiota. TMAO maintained its prognostic role also during follow-up. Left atrial (LA) enlargement is a hallmark of HF with preserved ejection fraction (HFpEF) and predicts disease severity and risk of adverse outcome. Reddy et al.8 evaluated the potential value of LA strain measurement in 378 patients with unexplained exertional dyspnoea who underwent echocardiography and invasive cardiopulmonary exercise testing. LA reservoir strain and conduit strain were impaired in HFpEF patients, compared to subjects with non-cardiac dyspnoea. LA reservoir strain showed the best accuracy, compared with all other echocardiographic indexes, including E/e', LA enlargement, LV hypertrophy and LV global longitudinal strain. Indexing LA reservoir strain to estimated LA pressure (E/e') as a surrogate for LA compliance further improved diagnostic performance. Thus, LA reservoir strain may provide better diagnostic accuracy beyond conventional echocardiographic measures to identify HFpEF patients. Consistent results were found in another study.9 Pellicori et al.10 recorded clinical, laboratory (N-terminal pro-BNP, NT-proBNP) and ultrasound signs of congestion, including lung B-lines, inferior vena cava (IVC) diameter, internal jugular vein diameter (JVD) before and after a Valsalva manoeuvre (JVD ratio), in 342 ambulatory patients with HF, 75% in New York Heart Association class I or II. Either clinical or ultrasound signs of congestion were detected in 242 (71%) of these patients. Amongst the 203 patients (59%) clinically free of congestion, 31 (15%) had ≥ 14 B-lines, 57 (29%) had a dilated IVC and 38 (20%) had an abnormal JVD ratio (< 4). During a median follow-up of 234 days, 60 patients (18%) died or were hospitalized for HF. NT-proBNP, IVC and JVD ratio were independent predictors of this composite outcome. Lung ultrasound has gained wide use for the detection of lung congestion in patients with both acute and chronic HF.11 However, high variability in the methods used have made comparisons difficult between different studies and practical indications. The consensus document of the Study Group on Acute Heart Failure of the Acute Cardiovascular Care Association and the HFA of the European Society of Cardiology12 gives practical guidance with respect of the equipment to use, number of chest zones to assess, method of quantification of B-lines, indications to additional investigations (e.g. BNP and echocardiography) and the impact on therapy. A checklist for scientific reporting is also provided. Adherence to evidence-based medical treatment remains a major unmet need and probably the best way to improve patient outcomes.13, 14 Komajda et al.15 report the long-term 18-month follow-up of their QUality of Adherence to guideline recommendations for LIFe-saving treatment in HF surveY (QUALIFY) study. The study was conducted in 6118 ambulatory HFrEF patients. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Physician adherence to guidelines was an independent predictor of HF deaths and of the composite of HF hospitalization or cardiovascular death at both univariable and multivariable analysis. Thus, physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines.16 The role of functional mitral regurgitation (FMR) as a cause or a mere consequence of LV remodelling and HF progression remains controversial. The two prospective, randomized, controlled trials recently concluded have not solved this controversy. Senni et al.17 have summarized current knowledge regarding the prevalence of FMR in HF patients, its detection and quantification, as well as the effects of optimal treatment with drugs and devices. They have then reviewed current results with MitraClip treatment including the results of the observational studies and the predictors of post-MitraClip outcomes. Finally, they have compared the design, patient characteristics, procedural results and outcomes of the two major prospective trials conducted to date.