Christos-Konstantinos Antoniou

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

AIMS The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population. METHODS AND RESULTS 161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n=50, 20mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n=56, 5mg/h and 5 μg kg(-1)min(-1) respectively), or c) low-dose furosemide (LDF, n=55, furosemide 5mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P=0.74) or at one year (38.1%, 33.9% and 32.7%, P=0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P=0.55) or one year (60.0%, 50.0%, and 47%, P=0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P<0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P=0.27). No significant differences in adverse events were noted. CONCLUSIONS In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.

T wave axis deviation and QRS-T angle – Controversial indicators of incident coronary heart events

Abnormal orientation of the T-wave axis and increased angle between the QRS complex (depolarization) and the T-wave (repolarization) have long been assumed to provide a global measure of repolarization abnormality, and have been used to assess ventricular repolarization. The ability of the T wave axis deviation and the QRS-T angle to predict incident coronary heart events was examined in several studies. However, conflicting results have led to significant controversy in the literature concerning their purported ability. Potential explanations involve true variation between study populations, non-standardized cut-off values, different baseline cardiovascular risk levels or different patterns of confounding by other concomitant cardiovascular risk factors. In the present article we will attempt to briefly present the rationale and pathophysiology behind these indices, summarize existing knowledge regarding their prognostic significance and their correlation with established cardiovascular disease risk factors. Further prospective studies are necessary to confirm or refute whether T-wave axis deviation, QRS-T angle and ventricular gradient may in the future serve as indicators of incident coronary heart events and mortality, both in populations with higher prevalence of subclinical advanced atherosclerotic heart disease and in apparently healthy subjects.

Arrhythmic risk stratification in non-ischemic dilated cardiomyopathy: Where do we stand after DANISH?

Publication of the DANISH randomized trial led to considerable debate, given that it demonstrated no survival benefit stemming from current implantable cardioverter-defibrillator (ICD) allocation criteria in patients with non-ischemic dilated cardiomyopathy (NIDCM). Consequently, a thorough reconsideration of our approach to sudden cardiac death (SCD)-risk stratification appears to be in order. NIDCM encompasses a wide spectrum of disease entities, often with differing arrhythmogenicity; however, in its kernel, is still defined by the fundamentals of electrophysiology that dictate that abnormal tissue, exhibiting altered electrophysiological properties is necessary for arrhythmogenesis, but not enough, given that formation of functional circuits is required. In this review article, we will attempt a presentation of the current status in SCD-risk stratification in NIDCM and introduce the concept of multifactorial tiered approach, bringing together non-invasive indices of arrhythmic potential and programmed ventricular stimulation, as an alternative approach, in order to finally delineate a potential basis for the design and realization of trials necessary to achieve a paradigm shift and improvement in NIDCM SCD-risk stratification.

Prevalence of late potentials on signal-averaged ECG in patients with psychiatric disorders

BACKGROUND Sudden cardiac death (SCD) occurs three times more often in psychiatric patients than in the general population. QRS fragmentation (QRSfr) and signal-averaged electrocardiography (SAECG) are simple, inexpensive, readily available tools for detecting the presence of abnormal depolarization and late potentials (LPs) in these patients, a result of either the underlying disease or treatment. METHODS Frequency of LP detection by SAECG and QRSfr was studied in 52 psychiatric patients and compared with 30 healthy (without known structural heart disease or occurrence of ventricular arrhythmia) controls. Patients were then prospectively followed up and incidence of SCD was recorded. RESULTS LP prevalence was significantly higher in patients than in controls (16/52-31% vs 2/30-7%, p=0.012), while QRSfr was similar between these two groups (p=0.09). Of the LP presence criteria, the root mean square value at terminal 40msec of the QRS (RMS40) was significantly lower in patients (32μV, SD=19μV, vs 46μV, SD=32μV, p=0.015). Among patients, no differences were noted between the LP positive and negative groups regarding age, sex, number of medications, class of antipsychotics and defined daily doses. Mean follow-up was 46months (SD=11) and during it 3 patients suffered SCD. Although 2 SCD victims had both LPs and QRSfr concurrently present, neither of them, nor their simultaneous presence could definitely account for the events. CONCLUSIONS LP prevalence in psychiatric patients was significantly higher than in controls. SAECG performance was feasible in all cases and constitutes a readily available tool for assessing myocardial electrophysiological alterations in this patient group.

Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy

BACKGROUND Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) in the context of primary prevention remains suboptimal. The purpose of this study was to examine the additional contribution of programmed ventricular stimulation (PVS) on established risk assessment. METHODS Two-hundred-and-three consecutive patients with diagnosed HCM and ≥1 noninvasive risk factors were prospectively enrolled over 19years. Patients were risk stratified, submitted to PVS and received an implantable cardioverter-defibrillator (ICD) according to then-current American Heart Association (AHA) guidelines and inducibility. Participants were prospectively followed-up for primary endpoint occurrence (appropriate ICD therapy or SCD). Contemporary (2015) AHA and European Society of Cardiology (ESC) guidelines were retrospectively assessed. RESULTS During a median follow-up period of 60months the primary endpoint occurred in 20 patients, 19 of whom were inducible and received an ICD. Overall, 79 patients (38.9%) were inducible and 92 patients (45.3%) received an ICD (PVS sensitivity=95%, specificity=67.2%, positive predictive value=24%, negative predictive value=99.2%). AHA and ESC guidelines application misclassified 3 and 9 primary endpoint-meeting patients, respectively. Inducibility was the most important determinant of event-free survival in multivariate Cox regression (hazard ratio=33.3). A combined approach of ESC score≥6% or AHA indication for ICD with PVS inducibility yielded absolute sensitivity and negative predictive value, the former at a more cost-effective and specific way. CONCLUSIONS Inducibility at PVS predicts SCD or appropriate device therapy in HCM. Non-inducibility is associated with prolonged event-free survival, while the procedure was proven safe. Reintegration of PVS into established risk stratification models in HCM may improve patient assessment.

Biomarkers Associated with Atrial Fibrosis and Remodeling

Atrial fibrillation is the most common rhythm disturbance encountered in clinical practice. Although often considered as solely arrhythmic in nature, current evidence has established that atrial myopathy constitutes both the substrate and the outcome of atrial fibrillation, thus initiating a vicious, self-perpetuating cycle. This myopathy is triggered by stress-induced (including pressure/volume overload, inflammation, oxidative stress) responses of atrial tissue, which in the long term become maladaptive, and combine elements of both structural, especially fibrosis, and electrical remodeling, with contemporary approaches yielding potentially useful biomarkers of these processes. Biomarker value becomes greater given the fact that they can both predict atrial fibrillation occurrence and treatment outcome. This mini-review will focus on the biomarkers of atrial remodeling (both electrical and structural) and fibrosis that have been validated in human studies, including biochemical, histological and imaging approaches.

Heart failure study of multipoint pacing effects on ventriculoarterial coupling: Rationale and design of the HUMVEE trial

Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies have revealed the potential role of multipoint pacing (MPP) in improving response and outcomes. The aim of this study is to compare the effects of MPP against those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii) quality of life, and (iv) NT‐proBNP levels and glomerular filtration rate (GFR) during a follow‐up of 13 months.

QT Prolongation and Malignant Arrhythmia: How Serious a Problem?

QT prolongation constitutes one of the most frequently encountered electrical disorders of the myocardium. This is due not only to the presence of several associated congenital syndrome but also, and mainly, due to the QT-prolonging effects of several acquired conditions, such as ischaemia and heart failure, as well as multiple medications from widely different categories. Propensity of repolarization disturbances to arrhythmia appears to be inherent in the function of and electrophysiology of the myocardium. In the present review the issue of QT prolongation will be addressed in terms of pathophysiology, arrhythmogenesis, treatment and risk stratification approaches. Although already discussed in literature, it is hoped that the mechanistic approach of the present review will assist in improved understanding of the underlying changes in electrophysiology, as well as the rationale for current diagnostic and therapeutic approaches.

Sustained ventricular tachycardia as a first manifestation of hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm in an elderly female patient

Sustained ventricular tachycardia complicating left ventricular apical aneurysms has been reported previously solely in middle‐aged patients with hypertrophic cardiomyopathy and mid‐cavity obstruction. We report a case of an elderly female patient who presented with incessant ventricular tachycardia as the first clinical manifestation of hypertrophic cardiomyopathy with mid‐ventricular obstruction and apical aneurysm.