Theodoros Kalos

Renal denervation therapy: Can it contribute to better blood pressure control in hypertension?

INTRODUCTION Although the first results from studies suggested important benefits regarding blood pressure (BP) control in resistant hypertension by the use of diverse systems of renal denervation (RDN) in the setting of resistant hypertension, the Symplicity HTN-3, randomized sham-controlled trial reduced the enthusiasm and led to a more critical approach towards this neuromodulation innovative therapy. Nowadays there is an ongoing research attempt to justify the pathophysiological background of RDN since overdrive of the sympathetic nervous system is one of the key mechanisms leading to the development and progression of the hypertensive and cardiovascular diseases. CONCLUSION Future RDN trials based on the clinical findings and gaps from previous works will try to identify those parameters to help identify better BP response, target the most suitable population and conclude whether this interventional approach can contribute to the clinical problem of uncontrolled hypertension.

Biomarkers of Atrial Fibrillation in Hypertension

BACKGROUND Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. METHOD We conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients. RESULTS Potential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. CONCLUSION The reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.

Uric acid as an independent predictor of coronary artery disease in essential hypertension: Data from an 8-year-follow-up study

The role of serum uric acid (SUA) in cardiovascular risk prediction remains to be further determined. We assessed the predictive value of SUA for the incidence of coronary artery disease (CAD) in 2287 essential hypertensive patients who were followed up for a mean period of 8 years. The distribution of SUA levels at baseline was split by the median (5.2 mg/dL) and subjects were classified into those with high and low values. Hypertensives who developed CAD (n = 57) compared to those without CAD at follow‐up (n = 2230) had at baseline higher SUA. In multivariate Cox regression model, among established confounders, high SUA (hazard ratio = 1.216, P = .016) turned out to be independent predictor of CAD. In essential hypertensive patients SUA independently predicts CAD.

Serum uric acid is independently associated with diastolic dysfunction in apparently healthy subjects with essential hypertension

OBJECTIVES Accumulating evidence suggests a direct role of Uric Acid (UA) on Left Ventricular (LV) diastolic function in chronic kidney disease and Heart Failure (HF) patients. Recently, UA has been linked to LV Hypertrophy (LVH) and Diastolic Dysfunction (DD) in women with preserved Ejection Fraction (pEF) but not in corresponding men. We sought to assess if UA could predict indices of DD in hypertensive subjects with pEF independently of gender. METHOD We consecutively recruited 382 apparently healthy hypertensive subjects (age: 61.7±10.7, women: 61.3%, median EF: 64%). In 318 patients in sinus rhythm, LV mass-indexed to body surface area-was calculated (LVMI). LVH was set as an LVMI >116g/m2 or 96 g/m2 in men and women, respectively. The ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (Em) was used as an approximation of mean left atrial pressure (E/Em). RESULTS UA [median (interquartile range): 5.4(2) mg/dl] independently predicted E/Em (adjusted coefficient: 1.01, p =0.026) while an interaction term between gender and UA was no significant (p=0.684). An ordinal score of DD was calculated taking into account increased E/Em, left atrium dilatation and LVH. Women with increased UA had 254% increased odds (adjusted OR=2.54, p=0.005) to be classified in the upper range of the DD score. CONCLUSION In hypertensive subjects without HF, UA is independently associated with the presence of DD in both genders and correlates with its severity in women. Further prospective studies are warranted to evaluate the association of UA with adverse cardiovascular outcomes in high-risk populations such as HF with pEF.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots

INTRODUCTION Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. CONCLUSION Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients.

DOES RENAL HAEMODYNAMICS RELATE WITH CARDIAC AND AORTIC HAEMODYNAMICS IN THE EARLY STAGES OF ESSENTIAL HYPERTENSION

Introduction: The relationship of renal haemodynamics with cardiac and aortic hameodynamics is still unclear. Hypothesis: We evaluated the relationship of increased renal resistive index (RRI) with Augmentation index (AIx) and cardiac haemodynamics by means of mitral annular early diastolic velocity (E/Ea) in untreated patients with essential hypertension. Methods: 76 newly diagnosed untreated non diabetic patients with stage I-II essential hypertension [35 males, aged 50 years, office blood pressure (BP) = 143/ 91 mm Hg], underwent ABPM, complete echocardiographic study for determination of E/Ea and blood sampling for assessment of metabolic profile. Moreover, data on renal resistive index (RRI), obtained by Doppler ultrasound sampling of the intrarenal arteries, as well as augmentation index (AIx), were retrospectively analyzed. Results: Based on the mean value of RRI (0.60), hypertensives were classified into those with high and low RRI. Hypertensives with high RRI values compared to those with low values were older (55.6±9.8 vs 44.4±11.6 years, p Conclusions: Increased vascular resistance of intrarenal arteries is associated with impaired aortic and cardiac haemodynamics, as reflected by increased AIx and E/Ea (lateral) values. RRI may be considered a useful surrogate of haemodynamics in essential hypertension.

LEFT VENTRICULAR MASS VERSUS PULSE WAVE VELOCITY AS PREDICTORS OF CORONARY ARTERY DISEASE IN PATIENTS WITH ESSENTIAL HYPERTENSION: DATA FROM A GREEK 6-YEAR-FOLLOW-UP STUDY

Background: The aim of the present study was to compare the predictive role of arterial stiffness and left ventricular mass index (LVMI) for the incidence of coronary artery disease (CAD) in essential hypertensive patients. Methods: We followed up 1033 essential hypertensives (mean age 55.6 years,

TCT-764 EFFECTS OF MULTIELECTRODE RENAL DENERVATION ON SYMPATHETIC NERVE ACTIVITY AND INSULIN RESISTANCE IN METABOLIC SYNDROME

BACKGROUND Clinical evaluation of renal denervation (RDN) as a therapy for uncontrolled hypertension continues. Current emphasis is on more rigorously controlled trials, including the controlling of technique variability and more efficient nerve inactivation. The Peregrine System Infusion Catheter is used to perform RDN via the delivery of alcohol into the perivascular space of the renal artery, directly targeting the sympathetic nerves. The technique and mode of action of denervation by alcohol may offer advantages over energybased approaches, and merit further assessment.

METABOLIC SYNDROME IS ACCOMPANIED BY INCREASED SYMPATHETIC NERVOUS SYSTEM ACTIVITY AND ARTERIAL STIFFNESS IN RESISTANT HYPERTENSION

Resistant hypertension is related to sympathetic overdrive and arterial stiffening, while there are scarce data whether metabolic syndrome further potentiates sympathetic activity and vascular abnormalities in this setting. The aim of this study was to assess the effect of the metabolic syndrome on

FAVORABLE EFFECTS OF IVABRADINE ON SYMPATHETIC OVERDRIVE AND ARTERIAL STIFFENING IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Hypertension and metabolic syndrome are related to sympathetic overdrive and arterial stiffening, while there are no data whether ivabradine modulates sympathetic activity and vascular abnormalities in this setting. The aim of this study was to assess the effect of ivabradine on muscle sympathetic