Christos Kontogiannis

Prolonged intra-aortic balloon pump support in biventricular heart failure induces right ventricular reverse remodeling

BACKGROUND Right ventricular dysfunction is associated with high morbidity and mortality in candidates for left ventricular assist device (LVAD) implantation or cardiac transplantation. METHODS We examined the effects of prolonged intra-aortic balloon pump (IABP) support on right ventricular, renal and hepatic functions in patients presenting with end-stage heart failure. RESULTS Between March 2008 and June 2013, fifteen patients (mean age = 49.5 years; 14 men) with end-stage systolic heart failure (HF), contraindications for any life saving procedure (conventional cardiac surgery, heart transplantation, LVAD implantation) and right ventricular dysfunction were supported with the IABP. The patients remained on IABP support for a mean of 73 ± 50 days (median 72, range of 13-155). We measured the echocardiographic and hemodynamic changes in right ventricular function, and the changes in serum creatinine and bilirubin concentrations before and during IABP support. Mean right atrial pressure decreased from 12.7 ± 6.5 to 3.8 ± 3.3 (P < 0.001) and pulmonary artery pressure decreased from 35.7 ± 10.6 to 25 ± 8.4 mmHg (P = 0.001), while cardiac index increased from 1.5 ± 0.4 to 2.2 ± 0.7 l/m(2)/min (P = 0.003) and right ventricular stroke work index from 485 ± 228 to 688 ± 237 mmHg × ml/m(2) (P = 0.043). Right ventricular end-diastolic diameter decreased from 34.0 ± 6.5 mm to 27.8 ± 6.2 mm (P < 0.001) and tricuspid annular systolic tissue Doppler velocity increased from 9.6 ± 2.4 cm/s to 11.1 ± 2.3 cm/s (P = 0.029). Serum creatinine and bilirubin decreased from 2.1 ± 1.3 to 1.4 ± 0.6 mg/dl and 2.0 ± 1.0 to 0.9 ± 0.5 mg/dl, respectively (P = 0.002 and P < 0.001, respectively). CONCLUSIONS Prolonged IABP support of patients presenting with end-stage heart failure and right ventricular dysfunction induced significant improvement in right ventricular and peripheral organ function.

Repetitive-incessant electrical storm triggered by early repolarization

Early repolarization syndrome (ERS) was originally considered a normal variant with benign outcome. However, recent studies have demonstrated that it can be linked to a considerable risk of life‐threatening arrhythmias and sudden cardiac death. We report a case with an extraordinary, extremely malignant clinical expression of ERS refractory to all antiarrhythmic drugs including quinidine. This case demonstrates real‐time changes of dynamic electrocardiogram (ECG) preceding a polymorphic ventricular tachycardia (VT)‐ventricular fibrillation (VF) and possible external factors triggering arrhythmia onset. Implantable cardioverter‐defibrillator (ICD) function was terminated 6 months after implantation due to multiple‐incessant electrical storm (ES). Catheter ablation was the definite treatment of this malignant entity.

Bone Metabolism in Chronic Heart Failure

Purpose: Chronic Heart Failure (HF) is complicated by bone loss and osteoporosis, which have been linked to hyperparathyroidism. We studied the bone metabolism and possible role of cytokines in patients suffering from HF. Methods and results: We measured bone alkaline phosphatase (BALP), C-telopeptides of type I collagen (β-CTx) and Interleukin-(IL) 6 in 60 men, 56 ± 11 years of age, suffering from chronic HF, and in 13 age-matched men free from HF. We also measured total body and femoral bone densitometry and parathyroid hormone (PTH). The β-CTx concentrations were significantly higher in men with than in men without HF. The concentrations of BALP (12.4 ± 4.9 vs. 9.9 ± 3 μg/l; P=0.03) and β-CTx (0.67 ± 0.35 vs. 0.33 ± 0.21 ng/ml; P<0.001) were significantly higher in patients in New York Heart Association (NYHA) functional classes III or IV than in patients in classes I or II. Moderately strong correlations were observed between β-CTx, BALP, PTH and bone densitometry measurements. Positive correlations were observed between NYHA functional classes and a) mean PTH (r2=0.19; P<0.001) and b) mean β-CTx (r2=0.30; P<0.001) concentrations. Moreover, increasing serum β-CTx and BALP concentrations were correlated with measurements consistent with decreasing bone mass and increasing severity of HF. IL-6 was also correlated with β-CTx, BALP and PTH, though not with measurements of bone density. Increased serum concentrations of IL-6 were correlated with the severity of HF. β-CTx was a strong predictor of adverse clinical events (hazard ratio 6.32; 95% confidence interval 1.8-22.5; P=0.005), including after controlling for other prognostic markers of chronic HF severity and measurements of bone densitometry. Conclusion: Chronic HF, particularly at advanced stages, was associated with an acceleration of bone turnover and uncoupling of bone formation and resorption. These changes in bone metabolism, among others, could be due to secondary hyperparathyroidism and the chronic inflammatory state associated with chronic HF. The increased osteoclastic activity observed in chronic HF was associated with a poor prognosis.

Abdominal fat tissue echogenicity: a novel marker of morbid obesity.

Purpose Menopause-related changes may affect regional but also morphological characteristics of adipose tissue. We sought to assess the clinical value of echogenicity of subcutaneous adipose tissue (SAT) and preperitoneal adipose tissue (pPAT) in postmenopausal women without cardiovascular disease. Methods In 244 consecutively recruited postmenopausal women, subclinical atherosclerosis was assessed in the femoral and carotid arteries by intima-media thickness (IMT) and atheromatous plaques using high-resolution ultrasonography. In 41 women with a second visit (median follow-up 41.5 months), carotid atherosclerosis was re-evaluated. Images of SAT and pPAT were ultrasonographically acquired, and their echogenicity was evaluated by grayscale mean (GSMn) using a dedicated software. A control group of 20 healthy premenopausal women was used for comparisons in fat echogenicity. Results SAT GSMn but not pPAT was higher in postmenopausal as compared with healthy premenopausal women and was independently associated with metabolic markers of adiposity including body mass index (BMI) and waist circumference (WC). SAT GSMn was associated with carotid IMT and the presence and number of atheromatous plaques [adjusted OR 2.44 and 2.32 per 1-SD increase in GSMn (95% CIs 1.55 to 3.93 and 1.55 to 3.45), respectively]. SAT GSMn conferred incremental value over traditional risk factors, insulin resistance, BMI, and WC for the detection of subclinical atherosclerosis. Increased baseline SAT GSMn was associated with increased rate of progression in carotid IMT. Conclusions SAT echogenicity may serve as a qualitative marker of adiposity, conferring incremental clinical value over BMI and WC in postmenopausal women. Further investigation is warranted to assess the utility of ultrasonography-derived fat echogenicity as a screening method for morbid obesity.

Chios mastic improves blood pressure haemodynamics in patients with arterial hypertension: Implications for regulation of proteostatic pathways

Chios mastic (CM) is the resin of Pistacia lentiscus var. chia, exclusively produced in the Greek Aegean island of Chios. Accumulating evidence suggests a cardioprotective role of this resin by way of its antioxidant and anti-inflammatory properties. These attributes may also convey favourable effects on prohypertensive mechanisms, but its impact on blood pressure (BP) haemodynamics has not been investigated in clinical or experimental settings. We therefore sought to assess the acute effects of CM on peripheral and aortic haemodynamics and associated changes in gene expression of molecules involved in pathways related to hypertension. The study population consisted of 27 consecutive eligible volunteers (13 hypertensive patients) who responded to a call for participation in the study. Exclusion criteria were history of cardiovascular disease, current treatment with statins, history of allergy to CM, current use of vitamins or antioxidant supplements, dieting at the time of the study, history of eating disorders, acute or chronic inflammatory disease and active cancer. All volunteers gave written informed consent. In a randomised double-blind case controlled crossover design, volunteers were assessed at two consecutive visits one week apart. Participants were randomly assigned to first visit oral administration of 2800mg of CM (four tablets of 700 mg IASIS pharma Hellas S.A., Athens, Greece) or placebo. At each visit, haemodynamic parameters were assessed at three distinct time points (baseline, 2 and 3 hours after administration). Haemodynamic assessment included non-invasive measurement of aortic systolic blood pressure (SBP) and diastolic blood pressure and aortic augmentation index normalised for heart rate at 75 bpm by using radial artery tonometry (Sphygmocor System; Atcor Medical, Sydney, Australia) as previously described. We also studied expression levels of genes involved in proteome stability, proteasome and chaperones, cellular pro-oxidant responses, mitochondrial– metabolic pathways and inflammation (Figure 1) using isolated peripheral blood mononuclear cells (PBMCs). Gene expression analysis was performed in samples from four hypertensive patients with available samples of isolated PBMCs and the highest observed decrease in peripheral SBP 2 hours after CM administration, and was compared to three control normotensive subjects without decrease in peripheral SBP after CM administration. Univariable and multivariable analyses using linear mixed models with random effects were implemented to assess the effect of CM administration on longitudinal changes in parameters of interest. Statistical analysis was performed using the STATA package, version 11.1 (StataCorp, College Station, TX, USA). The level of statistical significance was set at P< 0.05 except for multiple comparisons

The complex crosstalk between inflammatory cytokines and ventricular arrhythmias

HighlightsCytokines present a non‐linear relationship with arrhythmogenic potential of myocardium.Cytokines affect the autonomic innervation of the heart.Serum cytokine levels predict the occurrence of arrhythmia after infarction.Serum cytokine levels affect the outcome of Cardiac Resynchronization Therapy. Abstract The network of cytokines consists one of the most extensively studied signaling systems of human body. Cytokines appear to modulate pathogenesis and progress of many different diseases in the human body, particularly in regards to cardiovascular system. However, their effects on the electrical system of the heart has been neglected. Over the past decade, attemps to understand this relationship led to the uncovering of the direct and indirect effects of cytokines on action potential propagation and cell depolarization. This relationship has been depicted in clinical practice as serum levels of cytokines are increasingly associated with prevalence of ventricular arrhythmias either isolated or secondary to either a heart condition or a systemic auto‐immune disease. Thus, they present an appealing potential as a biomarker for prediction of arrhythmia generation, as well as the ourtcome of electrophysiological interventions.

Implications of aging in the treatment of complex arrhythmias

The failing myocardium is characterized by numerous inter-related perturbations at molecular, cell and tissue level. Notably, aged myocardium and heart failure (HF) share common pathophysiologic processes and accumulating evidence suggests that impairment of sympathetic nervous system may modulate the clinical course of both entities. Within the sympathetic nervous system, adrenergic receptors (ARs) and changes in regulation of their responses are considered the connecting link for both aging and cardiovascular disease. In particular, decreased β-AR responsiveness, increased circulating catecholamines, and overall hyposensitivity to adrenergic stress are common pathophysiologic derangements in cardiovascular aging and HF [1]. We have previously shown that oral propranolol is more efficient and faster than metoprolol in the treatment of patients with implantable cardioverter-defibrillator (ICD) who experience an electrical storm (ES). This was the first study to compare the efficacy of a nonselective (propranolol) versus a selective β-blocker (metoprolol) towards the management of complex ventricular arrhythmias in HF patients [2]. It is well known that the failing human heart activates compensatory mechanisms, among which increased sympathetic activity has a key role on effector signaling and downstream targets. Adrenergic receptors are divided in two classes: α and β. In terms of β-ΑRs, β1AR is primarily located in the myocardium while β2AR is widely distributed in multiple tissues and β3-AR is found in adipose tissue [3]. As further explained in the specific study, failing myocardium exhibits a progressive decrease in β1/β2 ratio that is attributed to selective down regulation of the β1 receptors. Propranolol may effectively block signal transductions from both β1 and -unblocked from metoprololupregulated β2 cardiac receptors. Given that HF patients are also characterized by increased age, it is tempting to speculate that the combined effect of myocardium disease and aging inflates β-AR stimulation and ES represents an extreme form of sympathetic overdrive that necessitates a more potent β-blocker for prompt and successful treatment. Along this line, protein kinase A (PKA) is an important mediator of signal transduction downstream of G-protein coupled receptors in response to cAMP. Protein kinase A is comprised of two regulatory subunits, RI and RII. As PKA (and in specific, RIIβ) declines with aging, the β-adrenergic pathEditorial

Novel approaches for the treatment of ventricular tachycardia

Ventricular tachycardia (VT) is a crucial cause of sudden cardiac death (SCD) and a primary cause of mortality and morbidity in patients with structural cardiac disease. VT includes clinical disorders varying from benign to life-threatening. Most life-threatening episodes are correlated with coronary artery disease, but the risk of SCD varies in certain populations, with various underlying heart conditions, specific family history, and genetic variants. The targets of VT management are symptom alleviation, improved quality of life, reduced implantable cardioverter defibrillator shocks, prevention of reduction of left ventricular function, reduced risk of SCD, and improved overall survival. Antiarrhythmic drug therapy and endocardial catheter ablation remains the cornerstone of guideline-endorsed VT treatment strategies in patients with structural cardiac abnormalities. Novel strategies such as epicardial ablation, surgical cryoablation, transcoronary alcohol ablation, pre-procedural imaging, and stereotactic ablative radiotherapy are an appealing area of research. In this review, we gathered all recent advances in innovative therapies as well as experimental evidence focusing on different aspects of VT treatment that could be significant for future favorable clinical applications.

Continuous internal counterpulsation as a bridge to recovery in acute and chronic heart failure

Cardiac recovery from cardiogenic shock (CS) and end-stage chronic heart failure (HF) remains an often insurmountable therapeutic challenge. The counterpulsation technique exerts numerous beneficial effects on systemic hemodynamics and left ventricular mechanoenergetics, rendering it attractive for promoting myocardial recovery in both acute and chronic HF. Although a recent clinical trial has questioned the clinical effectiveness of short-term hemodynamic support with intra-aortic balloon pump (IABP, the main representative of the counterpulsation technique) in CS complicating myocardial infarction, the issue remains open to further investigation. Moreover, preliminary data suggest that long-term IABP support in patients with end-stage HF is safe and may mediate recovery of left- or/and right-sided cardiac function, facilitating long-term weaning from mechanical support or enabling the application of other permanent, life-saving solutions. The potential of long-term counterpulsation could possibly be enhanced by implementation of novel, fully implantable counterpulsation devices.

EFFECTS OF A NOVEL IMPLANTABLE COUNTERPULSATION ASSIST DEVICE ON LEFT VENTRICULAR MECHANOENERGETICS: COMPARISON WITH THE INTRA-AORTIC BALLOON PUMP IN A PORCINE MODEL OF ACUTE HEART FAILURE

We have developed a novel implantable counterpulsation left ventricular (LV) assist device, the Pressure-Unloading Left Ventricular Assist Device (PULVAD). We compared the effects of PULVAD support on LV mechanoenergetics to those induced by the intra-aortic balloon pump (IABP) in a porcine model of