PracticeUpdate: Cardiology | Vol1 - No.2 - 2016

HEART FAILURE & TRANSPLANTATION

11

Left ventricular geometry predicts risk of sudden cardiac arrest in patients with severely reduced ejection fraction

Comment by Raul Mitrani, MD M arkers of structural heart disease such as left ven- tricular hypertrophy or abnormal left ventricular geometric patterns have been associated with increased risk of ventricular arrhyth- mias and/or implantable defibrillator shocks. This paper examined various left ventricular geometric patterns in adult patients with sudden car- diac arrest from the Oregon Sudden Unexpected Death Study and com- pared the prevalence of these pat- terns with those in a control group. The authors demonstrated that ec- centric hypertrophy, defined as an increased left ventricular mass index with normal relative wall thickness, was found in 40.7% of patients with sudden cardiac arrest compared with 25.7% of controls (P = 0.025). Furthermore, eccentric hypertrophy, but not concentric hypertrophy, was independently predictive of sudden cardiac arrest, with odds ratio of 2.15 (CI, 1.08–4.29; P = 0.03).

It would be interesting to determine whether

Left ventricular geometry and risk of sudden cardiac arrest in patients with severely reduced ejection fraction Journal of the American Heart Association Take-home message • In this study, 172 cases of sudden cardiac arrest (SCA) from the Oregon Sudden Unexpected Death Study and 74 geographic controls with no history of SCA and their archived echocardiograms were evaluated. This analysis included patients with LVEF ≤40%. SCA cases had significantly lower LVEF, fewer had normal LV geometry, and more had eccentric hypertrophy compared with controls. Eccentric hypertrophy was found to be predictive of SCA in a multivariate model. • These findings demonstrate the potential for improved SCA risk determination based on routine echocardiograms. Abstract

The implications of this study are that the risk for ventricular arrhyth- mias in patients with left ventricular dysfunction may be modulated by the type of ventricular remodelling. In the future, it would be interesting to determine whether therapies that restore left ventricular remodelling to a more normal geometry subse- quently lower arrhythmic risk. therapies that restore left ventricular remodelling to a more normal geometry subsequently lower arrhythmic risk.

of 246 subjects were included in the analysis. SCA cases (n=172, 68.6±13.3 years, 78% male), compared to controls (n=74, 66.8±12.1 years, 73% male), had lower LVEF (29.4±7.9% vs 30.8±6.3%, P=0.021). Fewer cases presented with normal LV geometry (30.2% vs 43.2%, P=0.048) and more with eccen- tric hypertrophy (40.7% vs 25.7%, P=0.025). In a multivariate model, eccentric hypertrophy was independently predictive of SCA (OR 2.15, 95% CI 1.08–4.29, P=0.03). CONCLUSIONS Eccentric LV hypertrophy was independently associated with increased risk of SCA in subjects with EF ≤40%. These findings, now consistent between device-im- planted and non-implanted populations, indicate the potential of improving SCA risk stratification from the same noninvasive echocardiogram at no additional cost. J Am Heart Assoc 2016;5:e003715, Phan D, Aro AL, Reinier K, et al.

BACKGROUND Recent reports indicate that specific left ven- tricular (LV) geometric patterns predict recurrent ventricular arrhythmias in patients with implantable cardioverter-defibril- lators and reduced left ventricular ejection fraction (LVEF). However, this relationship has not been evaluated among patients at risk of sudden cardiac arrest (SCA) in the general population. METHODS AND RESULTS Adult SCA cases from the Oregon Sudden Unexpected Death Study were compared with geographic controls with no prior history of SCA. Archived echocardiograms performed closest and prior to the SCA event were reviewed. LV geometry was defined as normal (normal LV mass index [LVMI] and relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT), or eccentric hypertrophy (increased LVMI and normal RWT). Analysis was restricted to those with LVEF ≤40%. A total

Dr Mitrani is Director of Clinical Cardiac Electrophysiology, and Director of the Cardiac Electrophysiology

Laboratory at University of Miami, Miller School of Medicine, Miami.

Unresolved hypochloraemia, diuretic resistance, and poor outcome in patients with acute HF

in the literature resonate with a very clear message: it is now time to come to a new point of sobriety. We know very little about salt in heart failure; before pursuing yet another elegant pathophysiological pathway leading to a new treatment “breakthrough,” maybe we should critically explore what we once thought was sacrosanct – sodium restriction in heart failure. It is time for a very different discovery paradigm in heart failure: salt – we need to know more. References 1. Ter Maaten JM, Damman K, Hanberg JS, et al Hypochloremia, Diuretic Re- sistance, and Outcome in Patients With Acute Heart Failure. Circ Heart Fail 2016;9:e003109. 2. Hanberg JS, Rao V, Ter Maaten JM, et al. Circ Heart Fail 2016;9:e003180. Dr Yancy is Vice Dean, Diversity & Inclusion, Magerstadt Professor of Medicine, Professor of Medical Social Sciences, Chief, Division of Cardiology, Northwestern University, Feinberg School of Medicine; Associate Director, Bluhm Cardiovascular Institute,

T he dictum in heart failure has always been that impaired so- dium handling is a fundamen- tal pathophysiological mechanism that contributes to symptomatic left ventricular dysfunction. Moreover, the bedrock of HF practice has been that excess sodium consumption exacerbates heart failure and sodium restriction alleviates heart failure. Yet, the evidence to support this dictum is less evident andmore empiric. It is, in fact, no longer heretical to suggest that sodium restriction is at best dubious in heart failure andmay even be harmful. Some among us have even explored salt administration as a therapeutic

Comment by Clyde Yancy, MD, MSc, MACC, FAHA, MACP

option and have argued the potential for benefit. Is there a truth embedded in this discombobulation? Perhaps a new dictum might be entertained. Chloride, as in “sodium chloride,” is not a passive electrolyte. Renal salt sensing is dependent on chloride rather than sodium, and an emerging class of chloride-sensitive kinases appear to establish a link between renal tubule sodium han- dling and neurohormonal activation. Newly published data by Testani and colleagues 1,2 stakes a new po- tential truth – hypochloraemia has a stronger association with clinical out- comes and diuretic resistance than failure (all P < 0.01). Newly developed hypochloraemia at day 14 was com- mon and associated with a decline in renal function and an increase in blood urea nitrogen (P < 0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03–1.10]; P < 0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloraemia at baseline that resolved was not associated with mortal- ity (P = 0.55), but new or persistent hy- pochloraemia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17–4.46]; P < 0.001). CONCLUSIONS Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloraemia 14 days later was independently associ- ated with reduced survival, whereas hypochloraemia that resolved by day 14 was not. Circ Heart Fail 2016;9:e003109, Ter Maaten JM, Damman K, Hanberg JS et al.

sodium, and repletion of chloride may reverse surrogates of diuretic resistance. However, this is not the eureka moment. The presented data do not establish causality, repletion of chloride does not improve outcomes as of yet, and hypochloraemia may be yet another epiphenomenon. But making a pivot along a more promis- ing path of investigation is a needed catalyst to address the data void that sodium chloride homeostasis in heart failure now represents. We are a long way from advising chloride supplements as treatment for heart failure. We should remain aligned with rigorous sodium restric- tion for those at risk for heart failure and reasonable sodium restriction for symptomatic patients. In the absence of evidence, we should resist non-ev- idence based approaches, including salt loading, as treatment for heart failure. But these data and multiple other data points and commentaries

Hypochloraemia, diuretic resistance, and outcome in patients with acute heart failure Circulation: Heart Failure Take-home message • The authors evaluated the association between chloride levels and diuretic responsiveness, decongestion, and mortality in 2033 patients hospitalised for acute heart failure (HF) in the PROTECT trial. Baseline hypochloraemia was associated with elevated bicarbonate, poor diuretic response, less haemoconcentration, and worsening HF. Hypochloraemia developing by day 14 was associated with declining renal function, increasing BUN (P < 0.01), and increased mortality (P < 0.001). • These data indicated that chloride measurement in acute HF patients at admission and at 14 days could be used as a marker for response to therapy and outcome.

Northwestern Memorial Hospital, Chicago, Illinois.

New drugs and devices listing

THERAPEUTIC GOODS ADMINISTRATION www.tga.gov.au Obinutuzumab (Gazyva) , Roche – Follicular lymphoma (extension of indications) Ixekizumab (Taltz) , Eli Lilly – Plaque psoriasis PHARMACEUTICAL BENEFITS SCHEME www.pbs.gov.au Exenatide (Bydureon) , AstraZeneca – Type 2 diabetes Pasireotide (Signifor LAR) , Novartis – Acromegaly Follitropin alfa (Bemfola) , Finox Biotech Australia – Ovarian stimulation, stimulation of spermatogenesis Tacrolimus (Tacrolimus Sandoz) , Sandoz – Adjunct to liver, kidney, lung or heart allograft transplantation Please consult the full Product Information before prescribing.

Abstract BACKGROUND Chloride plays a role in renal salt sensing, neurohormonal acti- vation, and regulation of diuretic targets, and hypochloraemia predicts mortality in acute heart failure (AHF). AHF thera- pies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF.

METHODS AND RESULTS Patients hos- pitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochlo- raemia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8±5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less haemo- concentration, and worsening heart

VOL. 1 • No. 2 • 2016