Renal Denervation in End-Stage Renal Disease: Current Evidence and Perspectives.

In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance.

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences±SD= 44±11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences±SD= 0±8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered.

Patients younger than 70 undergoing transcatheter aortic valve implantation: Procedural outcomes and mid-term survival.

INTRODUCTION: Based on recent data, the indication for transcatheter aortic valve implantation (TAVI) is expanding to individuals at lower surgical risk, who are generally younger than subjects historically treated for severe aortic stenosis. Indeed, younger patients have traditionally been under-represented in current TAVI literature. The aim of the present study is to report about clinical features, procedural outcomes and mid-term outcomes of patients younger than 70 who underwent TAVI in a single high-volume center. MATERIALS AND METHODS: Consecutive patients younger than 70 years of age who underwent TAVI for severe, symptomatic aortic stenosis between 2007 and 2019 at a single, tertiary referral center have been included in this retrospective study. Procedural and mid-term outcomes were analyzed, comparing 1st generation with 2nd generation devices. RESULTS: Between 2007 and 2019, 1740 TAVI procedures were performed in our center. Among these, one hundred twenty-nine (7.4%) patients were younger than 70 years at the time of the intervention and were included in the present analysis. Fifty-eight patients (45%) were implanted with a 1st generation prosthesis while seventy-one patients (55%) were implanted with a 2nd generation device. Reasons which lead to a transcatheter approach in this population were: previous CABG (27.9%); porcelain aorta (24%); severe left ventricular systolic dysfunction (21.7%); prior chest radiation (19.4%); severe lung disease (8.5%); hemodynamic instability (7.0%); advanced liver disease (4.6%) and active cancer (3.9%). Overall device success rate was 89%, with no differences among 1st and 2nd generation devices. Threeyears all-cause mortality was 34%, with no difference among the two groups. Low incidence of aortic-valve re-intervention was observed at mid-term follow-up (late valve re-intervention = 2.3%). CONCLUSIONS: TAVI in young patient with appropriate indication for intervention is a safe procedure, associated with low rate of in hospital mortality and low rate of severe complications both with 1st and with 2nd generation devices. When considering long term durability, more data are needed; in our case series long-term follow up shows a good survival and also an extremely low rate of valve re-intervention.

Ambulatory blood pressure monitoring by a novel cuffless device: a pilot study.

PURPOSE: Cuffless blood pressure (CL-BP) measurements are believed to be a potentially alternative to cuff-occlusion-based (C-BP) measurement. A new cuffless device was developed for ambulatory BP monitoring. We assessed the accuracy of a new CL-BP device compared to a standard oscillatory C-BP device over the 24 h. MATERIALS AND METHODS: Eighty-four consecutive patients were included in the study. BP was measured simultaneously by the CL-BP device and by a C-BP device over the 24 h. Calculations included 24 h mean systolic (S) BP, the mean diastolic (D) BP and the heart rate (HR). Correlations between the CL-BP and C-BP measurements were sought using Pearson's correlation coefficients and Bland-Altman plots. RESULTS: Using the C-BP device, the 24 h SBP value for the cohort was 125.4 ± 10.9 mmHg (mean ± SD); the corresponding DBP value being 75 ± 8.3 mmHg. Mean SBP/DBP were higher with the CL-BP device, i.e. 131.1 ± 15.9/80.2 ± 9.7 mmHg . The correlation coefficients between the two sets of values were significant (SBP: r = 0.58, DBP: r = 0.65). Better correlations for SBP and DBP were found 1) in patients with BMI > 25 (SBP: r = 0.65, DBP: r = 0.70) compared to those with BMI <25 and 2) in males compared to females (SBP: r = 0.71, DBP: r = 0.77). CONCLUSIONS: In our patients a CL-BP device estimated 24 h mean SBP and DBP differently from the classical oscillometric device, with a moderate correlation. CL-BP measurements were most accurate on male and overweight subjects.

Renal denervation in patients with end-stage renal disease and resistant hypertension on long-term haemodialysis.

INTRODUCTION: Recent randomized controlled trials have confirmed the ability of renal denervation to lower blood pressure (BP) in patients, resistant to the BP-lowering effect of multiple antihypertensive drug administration. Evidence is limited, however, in patients with end-stage renal disease (ESRD) and haemodialysis, a condition in which a persistent BP elevation, despite administration of many antihypertensive drugs, is common. Aim of the present study was to test the BP-lowering efficacy of renal denervation in patients with resistant hypertension and ESRD on haemodialysis. BP was measured repeatedly in the office and over the 24 h during 1-year follow-up. METHODS AND RESULTS: The study was conducted from February 2017 to January 2018 at the Policlinico of Monza, Monza, Italy. We included 24 men and women aged at least 20 years (mean 55 ±â€Š16) who had ESRD, were on long-term haemodialysis and exhibited resistant hypertension, that is, elevated office and ambulatory BP values, despite multidrug antihypertensive treatment (n = 5.4 ±â€Š1). We excluded patients with renal artery stenosis, malignancy, and a probable life expectancy less than 1 year. Twelve patients were included in the renal denervation and 12 in the medical treatment (control) group. All patients underwent office and 24 h ambulatory BP measurements at baseline and at 1, 6 and 12 months during the follow-up. In the renal denervation group, baseline office and 24 h mean SBP were 180 ±â€Š112 and 175 ±â€Š11 mmHg, respectively, the corresponding values in the control group being 181 ±â€Š19 and 181 ±â€Š20 mmHg. Most of the other baseline characteristics were also similar or only slightly different between groups, including the mean number of administered antihypertensive drugs at baseline. SBP showed an early and persistent reduction after renal denervation (office SBP: 165 ±â€Š13; 150 ±â€Š7 and 149 ±â€Š11mmHg; 24 h SBP 163 ±â€Š20, 148 ±â€Š10 and 149 ±â€Š17 mmHg after 1, 6 and 12 months, respectively). The BP-lowering effect was almost always present and statistically significant during both the day and night. DBP changes followed a similar pattern whereas heart rate never showed any significant change. No significant periprocedural complication of renal denervation was seen. The mean number of administered drugs did not show any significant BP change during the study. CONCLUSION: In ESRD patients under long-term haemodialysis in whom BP was markedly elevated despite administration of many antihypertensive drugs, renal denervation lowered both ambulatory and office BP. The reduction persisted over a 1-year follow-up.

Improvement of functional capacity in sacubitril-valsartan treated patients assessed by cardiopulmonary exercise test.

Neprilisin and angiotensin receptor inhibition (Sacubitril/Valsartan, i.e. ARNI) is recommended in heart failure guidelines for patients in NYHA class II-III with reduced left ventricular ejection fraction (LVEF). ARNI increase survival and quality of life; due to their hemodynamic effects, ARNI could also affect exercise tolerance. We studied the effects of ARNI on cardiopulmonary test (CPET) after six months of treatment in 35 patients [67 ± 11 years; LVEF 31 ± 6%; NT-proBNP 1822 ± 1651 pg/ml; ICD/CRT since at least 6 months in 26/35], treated with increasing doses of Sacubitril/Valsartan up to 318 ± 36 mg/die. In addition, levels of NT-proBNP, renal function, electrolytes, and echocardiocolorDoppler were assessed in the same time periods. No variations of renal function and/or potassium levels were observed; NT-proBNP decreased. Most CPET variables were improved by ARNI (p < .05): peak VO2 and O2 pulse increased (from 15.8 ± 3.4 to 17.0 ± 4.0 ml/kg/min and from 11.5 ± 2.5 to 12.6 ± 2.4 ml/beat, respectively), while VEVCO2 slope decreased from 35.2 ± 11.2 to 33.1 ± 12.3. A significant relationship (p < .05) was observed between the amount of increase in LVEF and that of O2 pulse in all patients, and between the amount of decrease in PAPs and that of VEVCO2 slope in patients showing pulmonary hypertension in baseline. In a subgroup of 22 patients who already completed A 1 year follow-up, overall CPET improvement was maintained. In conclusion, already in the short term ARNI favourably affect cardiopulmonary response to exercise in heart failure patients; such a change seems to be preserved on a longer period.

Noninvasive Estimation of Aortic Stiffness Through Different Approaches.

Aortic pulse wave velocity is a worldwide accepted index to evaluate aortic stiffness and can be assessed noninvasively by several methods. This study sought to determine if commonly used noninvasive devices can all accurately estimate aortic pulse wave velocity. Pulse wave velocity was estimated in 102 patients (aged 65±13 years) undergoing diagnostic coronary angiography with 7 noninvasive devices and compared with invasive aortic pulse wave velocity. Devices evaluating carotid-femoral pulse wave velocity (Complior Analyse, PulsePen ET, PulsePen ETT, and SphygmoCor) showed a strong agreement between each other ( r>0.83) and with invasive aortic pulse wave velocity. The mean difference ±SD with the invasive pulse wave velocity was -0.73±2.83 m/s ( r=0.64) for Complior-Analyse: 0.20±2.54 m/s ( r=0.71) for PulsePen-ETT: -0.04±2.33 m/s ( r=0.78) for PulsePen ET; and -0.61±2.57 m/s ( r=0.70) for SphygmoCor. The finger-toe pulse wave velocity, evaluated by pOpmètre, showed only a weak relationship with invasive aortic recording (mean difference ±SD =-0.44±4.44 m/s; r=0.41), and with noninvasive carotid-femoral pulse wave velocity measurements ( r<0.33). Pulse wave velocity estimated through a proprietary algorithm by BPLab (v.5.03 and v.6.02) and Mobil-O-Graph showed a weaker agreement with invasive pulse wave velocity compared with carotid-femoral pulse wave velocity (mean difference ±SD =-0.71±3.55 m/s, r=0.23; 1.04±2.27 m/s, r=0.77; and -1.01±2.54 m/s, r=0.71, respectively), revealing a negative proportional bias at Bland-Altman plot. Aortic pulse wave velocity values provided by BPLab and Mobil-O-Graph were entirely dependent on age-squared and peripheral systolic blood pressure (cumulative r2=0.98 and 0.99, respectively). Thus, among the methods evaluated, only those assessing carotid-femoral pulse wave velocity (Complior Analyse, PulsePen ETT, PulsePen ET, and SphygmoCor) appear to be reliable approaches for estimation of aortic stiffness.

A new Percutaneous technique for effective vascular Access Site closure in patients undergoing Transfemoral aortic valve implantation and thoraco-abdominal aortic aneurysm rEpair: the PASTE study.

AIMS: The success of transfemoral transcatheter aortic valve implantation (TAVI) and thoraco-abdominal aneurysm repair (TAAR) depends on haemostatic control of the access site, which is usually obtained with suture-based closure devices (Prostar or two ProGlide). A single ProGlide/Glubran technique, involving a suture placement on the vessel wall followed by tissue glue injection around the vessel wall, has not been previously investigated in this clinical setting. Our aim was to study the feasibility and safety of a single ProGlide/Glubran technique for vascular access-site closure after transfemoral TAVI and TAAR. METHODS AND RESULTS: This technique was used in 250 patients from 2012 to 2017. The primary endpoint was the success of the technique, defined as access-site haemostasis without complications and not requiring any additional intervention within 30 days of the index procedure. Patients had a mean age of 82.4±1.93 years, with a logistic EuroSCORE of 20.2±2.32. A total of 218 TAVI and 32 TAAR procedures were performed with a mean sheath size of 18.09±1.55 Fr. The mean sheath to femoral artery ratio was 1.04±0.16, with mean femoral artery minimal lumen diameter 6.65±0.64 mm. The overall success rate of this technique was 98.4%. Four patients (1.6%) developed critical stenosis of the femoral artery requiring balloon dilatation. No major VARC-2 vascular complications were observed. Thirty-day mortality was 0.4% (non-cardiovascular). CONCLUSIONS: The results of this study suggest that the single ProGlide/Glubran technique is a safe and effective method of closing the arterial access site after transfemoral TAVI and TAAR. The results of our study need to be confirmed in a randomised controlled trial before being adopted in routine clinical practice.

Long-Term Contrast Echocardiography and Clinical Follow-Up after Percutaneous Closure of Patent Foramen Ovale Using Two Different Atrial Septal Occluder Devices.

INTRODUCTION: Percutaneous patent foramen ovale (PFO) closure by means of a septal occluder device (SOD) is a well-known therapeutic strategy for the secondary prevention of paradoxical embolic neurological events. The aim of this study was to provide long-term echocardiographic and clinical follow-up data on patients who had undergone percutaneous PFO closure with 2 different SOD. METHODS: We selected 2 groups of patients treated with 2 different SOD: Group A: 52 patients with an Amplatzer(®) PFO Occluder and Group B: 49 patients with a Figulla Flex(®) device. All patients underwent follow-up Bubble Test Transthoracic Echocardiography (BTTE) and clinical examination. The results were compared with those recently reported in a group of patients with similar characteristics, but that had been treated conservatively, which acted as a control group. RESULTS: The mean follow-up after PFO closure was 53 months. The Amplatzer(®) PFO Occluder and the Figulla Flex were used in 52 (51.5%) and 49 (48.5%) of patients, respectively. We found no significant difference in the rate of effective PFO closure between the devices: Amplatzer 91.4%, Figulla 93.9% (P = 0.71). One patient (1.0%) suffered a recurrent neurologic event. BTTE was positive (BTTE+) in 8 patients (8%), 5 with an Amplatzer, and 3 with a Figulla device (P = 0.516). Only 1 patient with BTTE+ had a recurrent TIA (12.5%). No significant relationship was found between device dimensions and BTTE+ (P = 0.062). In the control group (163 patients), the recurrence of neurologic events was 9.2% (15 events), that was significantly higher in respect to the patients who had undergone percutaneous closure of the PFO. CONCLUSIONS: Percutaneous PFO closure was associated with a remarkably low risk of recurrent embolic neurological events, and no long-term device-related major complications. No statistically significant difference emerged between the 2 different SODs regarding BTTE positivity. Long-term follow-up showed that the recurrence of neurological events has been significantly higher in the group treated in a conservative way.

Predictors of carotid occlusion intolerance during proximal protected carotid artery stenting.

OBJECTIVES: The aim of this study was to identify predictors of occlusion intolerance (OI) developing during proximal protected carotid artery stenting (CAS). BACKGROUND: The use of proximal embolic protection devices, such as endovascular occlusion, during CAS has been demonstrated to be particularly safe and effective. However, endovascular occlusion can expose the ipsilateral hemisphere to hypoperfusion and produce transient neurological symptoms (OI). METHODS: From March 2010 to March 2012, 605 consecutive patients underwent proximal protected CAS at our institution. To identify independent predictors of OI, a multivariate logistic regression model was developed that included all patients' clinical/angiographic and procedural characteristics. RESULTS: OI developed in a total of 184 patients (30.4%). Compared with patients in whom OI did not develop, those who experienced OI had lower occlusion pressure (OP) (42.3 ± 12.7 mm Hg vs. 61.9 ± 15.4 mm Hg, p < 0.001). Receiver-operating characteristic curve analysis demonstrated that OP was the most consistent predictor of OI with a C-statistic of 0.85 (95% confidence interval [CI]: 0.82 to 0.88) with best cutoff being ≤40 mm Hg (sensitivity, 68.5%; specificity, 93.3%). By logistic regression analysis, the most powerful independent predictor of OI developing was an OP ≤40 mm Hg (odds ratio: 33.2, 95% CI: 19.1 to 57.7) and the most powerful clinical predictor of such OP was the presence of contralateral internal carotid artery occlusion (odds ratio: 3.1, 95% CI: 1.5 to 6.2). CONCLUSIONS: OI may occur in as many as one-third of the patients undergoing proximal protected CAS. This event is more common in those patients with an OP ≤40 mm Hg. Patients presenting with concomitant occlusion of the contralateral internal carotid artery more frequently have an OP ≤40 mm Hg.

Physical activity in the prevention of peripheral artery disease in the elderly.

Aging is a well-known cardiovascular risk factor and cardiovascular diseases (CVD) are estimated to be the most common cause of death in the elderly. Peripheral arterial disease (PAD) represents an important clinical manifestation of CVD leading to increase morbidity and mortality, especially in elderly population. The correct management of PAD population includes the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication. Progressive physical activity is an effective treatment to improve walking distance and to reduce mortality and cardiovascular events in patients with PAD, however the ability to effectively engage in physical activity often declines with increasing age. The maintenance and increase of reserve functional capacity are important concepts in the elderly population. Ultimately, the goal in participation of physical activity in the healthy elderly population is maintenance and development of physical functional reserve capacity. Therefore, for individuals suffering of PAD, appropriate physical activity in the form of supervised exercise may serve as a primary therapy. Although there are few direct comparisons of therapeutic exercise programs vs. pharmacological or surgical interventions, these increases in walking distance are greater than those reported for the most widely used agents for claudication, pentoxyphylline, and cilostazol. Despite a reduction in mortality and improvement of quality of life caused by physical activity in the PAD population, the molecular, cellular, and functional changes that occur during physical activity are not completely understood. Therefore, this review article aims at presenting an overview of recent established clinical and molecular findings addressing the role of physical activity on PAD in the older population.

Transradial approach for the endovascular treatment of type I endoleak after aortic aneurysm repair: a case report.

BACKGROUND: Endovascular repair of aortic aneurysms (EVAR) is obtained through the positioning of an aortic stent-graft, which excludes the aneurysmatic dilation. Type I endoleak is the most common complication, and it is caused by an incompetent proximal or distal attachment site, causing the separation between the stent-graft and the native arterial wall, and in turn creating direct communication between the aneurysm sac and the systemic arterial circulation. Endoleak occurrence is associated with high intrasac pressures, and requires a quick repair to prevent abdominal aortic aneurysm rupture. CASE PRESENTATION: We report the first case of a 80-year-old man undergoing percutaneous closure of a peri-graft endoleak (type I) by transcatheter embolization through radial arterial access. CONCLUSION: The transradial approach has been shown to be a safe and effective alternative to the traditional transfemoral approach. A decrease in vascular complications and improved patient comfort are the primary benefits of this technique in patients with previous EVAR.

Abdominal aortic aneurysm in patients affected by intermittent claudication: prevalence and clinical predictors.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a frequent cause of death among elderly. Patients affected by lower extremity peripheral arterial disease (LE-PAD) seem to be particularly at high risk for AAA. We aimed this study at assessing the prevalence and the clinical predictors of the presence of AAA in a homogeneous cohort of LE-PAD patients affected by intermittent claudication. METHODS: We performed an abdominal ultrasound in 213 consecutive patients with documented LE-PAD (ankle/brachial index ≤ 0.90) attending our outpatient clinic for intermittent claudication. For each patient we registered cardiovascular risk factors and comorbidities, and measured neutrophil count. RESULTS: The ultrasound was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females, mean age 65.9 ± 9.8 yr) entered the study. Overall, AAA was present in 19 patients (9.0%), with a not significant higher prevalence in men than in women (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 ± 7.0 vs 65.4 ± 9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p = 0.027), and greater neutrophil count (5.5 [4.5 - 6.2] vs 4.1 [3.2 - 5.5] x 10(3)/µL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73, 95% CI 0.60 - 0.86, p = 0.010) was higher than that for age (0.67, CI 0.56-0.78, p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count ≥ 5.1 x 10(3)/µL (cut-off identified at ROC analysis) was as high as 29.0%. CONCLUSIONS: Prevalence of AAA in claudicant patients is much higher than that reported in the general population. Ultrasound screening should be considered in these patients, especially in those with an elevated neutrophil count.