Effects of Renal Sympathetic Denervation in Diastolic Heart Function in CKD Refractory Hypertensive Patients

Sympathetic activation promotes hypertension and induces cardiac hypertrophy, besides being directly proportional to deterioration of renal function.1-6 Studies including participants with mild to moderate reduction in estimated glomerular filtration rate (eGFR) showed an independent association between chronic kidney disease (CKD) and left ventricular hypertrophy (LVH).7-10 Specifically, there is a progressive increase in the prevalence of LVH and increased left ventricular mass when the eGFR decreases. LVH and cardiac fibrosis have been linked to increased risk of sustained ventricular arrhythmias and predisposition to sudden cardiac death (SCD).11-15

][9][10] Specifically, there is a progressive increase in the prevalence of LVH and increased left ventricular mass when the eGFR decreases.[13][14][15] Presently, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e′ ratio) is used for the evaluation of left ventricular filling pressure, and it has been used as a marker to diagnose diastolic heart failure (HF). 16,17In hypertensive patients with elevated E/e′ ratio the annual mortality rate is 10% and the ratio is considered to be a prognostic factor for the development of cardiovascular disease (CVD). 18Diastolic HF is an important factor that increases mortality related to the cardiovascular system in patients with CKD whose extent of kidney function deterioration differs. 19As a non-invasive method to allow early assessment, the E/e' ratio estimated by tissue Doppler imaging can predict mortality and cardiovascular events in CKD patients with diastolic dysfunction.
The current study evaluated 15 patients with CKD and LVH who were selected according to a previously published protocol [20] .The Committee of Ethics in Research of the Medical School of Universidade Federal Fluminense approved the study and written informed consent was obtained from every patient.In the period from June 2011 to December 2012, thirty consecutive patients underwent renal sympathetic denervation (RSD).All of them had resistant hypertension and CKD (stages 2, 3 and 4), as shown in table 1.They underwent laboratory tests and assessment of renal function at baseline and 24 hours post procedure, before discharge.
The procedures were performed in the catheterization laboratory with direct visualization using fluoroscopy and radiopaque contrast.In several cases, we also used threedimensional mapping system EnSite Velocity (St.Jude Medical, St. Paul, Minnesota, USA) for construction of renal arteries and aorta anatomy, as well as for radiofrequency application in the selected sites.All patients remained under unconscious sedation.Patients were discharged after 24 hour hospitalization, clinically stable, walking without difficulty.Bruising or aneurismal formation was not seen at the puncture site.According to the protocol, 20 in the follow-up period, Doppler ultrasound of the renal arteries was performed one and 6 months after the procedure in all patients and did not show any complication or change in blood flow.
Left ventricular mass (LVM) assessed by echocardiography at baseline and 6 months post procedure was calculated from LV linear dimensions using the equation of Devereux. 21,22The left ventricular mass was indexed to body surface area (g/m2), as described. 21,23VH was considered present when LV mass exceeding 115 g/m2 for men and 95 g/m2 for women was observed. 21e changes at the 6th month after RSD in mean office systolic/ diastolic blood pressure, mean systolic/diastolic ambulatory blood pressure measurements (ABPM), average number of antihypertensive drugs, mean creatinine values, mean eGFR, albumin:creatinine ratio (ACR), and in LVM indexed to body surface area were already previously reported by our group, as shown in table 2.
Mechanical global left ventricular (LV) dyssynchrony reflected as prolonged total isovolumic time (t-IVT) has been introduced as a potential mechanism behind compromised stroke volume in HF.It has also been shown to be superior to other markers of dyssynchrony in predicting response to cardiac resynchronization therapy (CRT).Patients with HF with preserved ejection fraction (HFpEF) have exaggerated global mechanical dyssynchrony shown by prolonged t-IVT, compared with healthy age and gender matched controls.The relationship between t-IVT, LV filling and stroke volume suggests an association, more important than with ejection fraction or electrical dyssynchrony. 24In the present study, we reported for the first time the improvement in diastolic parameters measured by echocardiography in CKD patients with resistant hypertension and left ventricular hypertrophy 6 months after RSD.Our results suggest that the renal artery ablation in this kind of patients seems to avoid the progression to diastolic heart failure, as well as, seems to be effective in reducing lesions of target organs such as the heart and kidneys.

Figure1.
Figure1.(A) Isovolumic relaxation time measured in ms, (B) mitral valve lateral E/é, (C) mitral valve E deceleration time measured in ms, and (D) left atrial diameter measured in mm, all at baseline and 6 months after renal sympathetic denervation (n=15).Values are presented as mean ± SD.

Table 1 .
General features of the patients at baseline