Pascal Delsart

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial

BACKGROUND Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. METHODS The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. FINDINGS Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. INTERPRETATION In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. FUNDING French Ministry of Health.

Single-centre Prospective Comparison Between Contrast-Enhanced Ultrasound and Computed Tomography Angiography after EVAR

AIM To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to CT-angiography (CTA) for endoleak detection and aneurismal sac diameter measurement in the follow-up after endovascular abdominal aortic aneurysm repair (EVAR). METHODS From January 2006 to December 2010, 395 patients underwent EVAR follow-up with both CTA and CEUS. The diameter of the aneurismal sac and the presence of endoleaks were evaluated in all the 395 paired examinations. RESULTS Bland-Altman plots showed a good agreement in aneurismal sac diameter evaluation between the two imaging modalities. The mean diameter was 54.93 mm (standard deviation (SD) ±12.57) with CEUS and 56.01 mm (SD ± 13.23) with CTA. The mean difference in aneurismal sac diameter was -1.08 mm ± 3.3543 (95% confidence interval (CI), -0.75 to -1.41), in favour of CTA. The number of observed agreement in endoleak detection was 359/395 (90.89%). The two modalities detected the same type I and type III endoleaks. McNemars χ(2) test confirmed that CTA and CEUS are equivalent in endoleak detection. CONCLUSIONS CEUS demonstrated to be as accurate as CTA in endoleak detection and abdominal aortic aneurysm diameter measurements during EVAR follow-up, without carrying the risks of radiation exposure or nephrotoxicity. Even if it cannot be proposed as the sole imaging modality during follow-up, our analysis suggests that it should have a major role.

Renal resistance index and its prognostic significance in patients with heart failure with preserved ejection fraction

BACKGROUND Functional renal impairment is a common feature of heart failure with preserved ejection fraction (HFpEF). The link between functional renal impairment and HFpEF remains incompletely understood. With hypertension and diabetes as frequent co-morbidities, patients with HFpEF are at risk of developing intra-renal vascular hemodynamic alterations that may lead to functional renal impairment and impact on prognosis. METHODS Renal resistive index (RRI) was non-invasively determined by Doppler ultrasonic examination in 90 HFpEF patients and 90 age- and sex-matched hypertensive patients without evidence of heart failure (HF) who served as controls. Clinical, laboratory and cardiac echocardiography data were obtained in HFpEF patients and controls. To investigate its possible clinical relevance, RRI was evaluated as a prognostic index of all-cause mortality and hospitalization for HF. RESULTS Mean RRI was substantially greater in HFpEF patients than in controls (P < 0.0001), while mean blood pressure, glomerular filtration rate, hemoglobin and serum protein levels were significantly lower in HFpEF patients than in controls. On multivariable analysis, mean RRI was independently associated with HFpEF. In addition, increased mean RRI was an independent predictor of poor outcome [hazard ratio = 1.06 95% confidence interval (1.01-1.10), P = 0.007] and remained significantly associated with the outcome after adjustment for univariate predictors that included low mean blood pressure, low hemoglobin concentration and low glomerular filtration rate. Conclusion. Patients with HFpEF exhibit intra-renal vascular hemodynamic alterations. The severity of intra-renal vascular hemodynamic alterations correlates with a poor outcome.

Contrast-Enhanced Ultrasound vs. CT Angiography in Fenestrated EVAR Surveillance: A Single-Center Comparison

Purpose To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to computed tomographic angiography (CTA) during follow-up after fenestrated endovascular aneurysm repair (EVAR) of juxtarenal aortic aneurysms. Methods Between January 2008 and April 2011, 62 patients (all men; mean age 72 years) underwent fenestrated EVAR follow-up with both CTA and CEUS. In a retrospective analysis, the first CTA and CEUS postoperative examinations after EVAR were compared for endoleak detection, aneurysm sac diameter, and target vessel patency. The examinations were performed within 30 days of the procedure and the interval between the 2 scans was <7days. Only fenestrated endografts with up to 3 fenestrations (with or without a scallop) were eligible so that the entire implant could be visualized with standard abdominal ultrasound. Results The mean diameters of the aneurysm sac were 56.58 ± 8.56 mm with CEUS and 57.70 ± 8.59 mm with CTA. The mean difference in aneurysm sac diameter was –1.13 ± 3.19 mm (95% CI –0.34 to –1.92), with CTA measurements tending to be slightly larger. Bland-Altman plots showed good agreement between the imaging modalities with respect to aneurysm sac diameter (Spearman correlation coefficient rs=0.921, p<0.01). Endoleaks were detected by CTA in 7 (11.3%) of 62 patients and by CEUS in 6 (9.7%). In 59 (95.16%) cases, the tests agreed, and their equivalence was confirmed by binomial distribution testing. There was complete agreement between CEUS and CTA in the assessment of target vessels (144/146 patent target arteries; 1 had a significant stenosis and another was thrombosed). Conclusion CEUS is as accurate as CTA in endoleak detection, abdominal aortic aneurysm diameter measurement, and the evaluation of target vessels during surveillance of fenestrated stent-grafts. Although it cannot yet be proposed as the only imaging modality during follow-up, CEUS could be usefully employed with the self-evident advantage of reducing lifetime exposure to ionizing radiation.

Thrombocytopenia: an early marker of late mortality in type B aortic dissection

Mid-term and long-term mortality after aortic dissection remain high and due to unknown factors. To determine predicting factors at the acute phase associated with mid- and long-term all-cause mortality, patients with type B aortic dissection including intramural hematoma, treated in one referral university center in an area with a population of 4 million, were analyzed over a period of 12 years (from 1996 to 2008). Based on the total population, 77 patients discharged after type B aortic dissection (including 11 intramural hematoma) were recorded as treated with either medical treatment alone (n = 41) or with additional endovascular therapy (n = 36). The mean follow-up period was 50.8 months, with a survival rate of 78 % (17 deaths). Patient history, symptoms, medical treatment, biological parameters, imaging, and intervention during acute phase (more than 150 parameters) were analyzed to identify any relationship with complications and death. Kaplan–Meier survival curve and Cox proportional hazards analyses identified independent predictors of follow-up mortality from any cause. Factors influencing mortality (P < 0.05) were a low systolic blood pressure (SBP) at admission, a thrombocytopenia in the acute period, chronic bronchitis, diameter of ascending aorta, and renin–angiotensin system inhibitor intake. Independent predictors of mortality were chronic bronchitis (P = 0.0022, hazard ratio (HR) 17.5), early thrombocytopenia (P = 0.042, HR 3.5), and admission SBP <120 mmHg (P = 0.0048, HR 7.928). Treated (medical ± endovascular) type B aortic dissection held a worse long-term prognosis, which can be correlated with predicting factors, especially in-hospital thrombocytopenia, and should require closer follow-up

Predictors of poor blood pressure control assessed by 24 hour monitoring in patients with type B acute aortic dissection

The chronic management of post-acute aortic dissection (AD) of the descending aorta (Type B) is based on optimal control of blood pressure (BP), with a target BP < 135/80 mmHg. The aim of our study was to determine and verify effective blood pressure control with an objective measurement method and to identify predicting factors. Methods We collected data from 26 patients hospitalized in the acute phase of a Type B AD between 2006 and 2009. Two groups were defined according to 24 hour BP monitoring results at follow-up. Group 1 consisted of patients with a controlled BP (<130/80 mmHg), and Group 2 consisted of patients with an uncontrolled BP. Results Thirty four percent of patients showed an uncontrolled BP at checkup. Vascular history before AD (P = 0.06), high baseline BP trend (P = 0.01 for systolic and P = 0.08 for diastolic), and greater diameter of the descending aorta (P = 0.02) were associated with poor BP control. Conclusion Prognosis after AD is associated with BP control. Therefore, 24 hour BP monitoring can be made.

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index (P=0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P=0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

Background The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped‐care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. Methods and Results This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline‐adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was −10.1 mm Hg (P=0.0462) in the lowest tertile and −2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (−8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640). Conclusions RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Secondary medical prevention and clinical outcome in coronary artery disease patients with a history of non-coronary vascular intervention: A report from the CORONOR investigators

Aim To assess the level of secondary prevention and the outcome of coronary artery disease (CAD) in patients who have a history of non-coronary vascular intervention. Background Patients with polyvascular disease have been reported to receive less evidence-based medications, with worse risk factor control and to be at higher risk than patients with single-bed disease. It is unknown whether these findings remain valid in the modern era of secondary prevention. Methods We included 4184 patients with stable CAD. Two groups were formed according to the absence (n = 3704) or presence (n = 480) of a history of non-coronary vascular intervention. Treatments and risk factor control were recorded at inclusion. Follow-up was performed after 2 years. Results Antiplatelets, angiotensin system antagonists, beta-blockers and statins were widely prescribed in both groups. The number of antihypertensive drugs was higher in patients with non-coronary vascular intervention. Except for slight increases in the rate of current smokers and in systolic blood pressure, risk factor control was similar between groups. All-cause and cardiovascular mortality rates were higher in patients with non-coronary intervention with adjusted HR of 1.55 (1.13–2.13) (p = 0.007), and 1.98 (1.24–3.15) (p = 0.004), respectively. Conclusions In modern practice and real life conditions, the higher risk of CAD patients with a history of non-coronary vascular intervention is taken into account, with more intense secondary prevention and similar risk factor control than patients without such history. In spite of the level of secondary prevention, patients with a history of non-coronary vascular intervention remain at high risk of cardiovascular events. This should be an incentive to discuss more stringent objectives for secondary prevention in patients with polyvascular disease.

Should we screen for masked hypertension in patient with vascular disease

Background: The influence of hypertension on cardiovascular risk is well known. Ambulatory blood pressure measurement (ABPM) is able to identify patients with masked hypertension (MH) underdetected by clinical BP measurement. The benefit of screening for MH in a high-risk population was investigated. Aims: To detect MH in a population with no prior history of hypertension and medically treated for peripheral or coronary arterial disease. Methods: Thirty-eight consecutive patients with peripheral or coronary artery disease documented with arteriography, without a history of hypertension, and with an admission BP < 140/90 mmHg underwent ABPM after discharge. Ambulatory BP ≥ 125/80 mmHg were defined as MH. Results: MH was found in 11 patients (28.9%). The MH group had a mean systolic and diastolic hospitalization BP significantly higher (127 versus 115 mmHg, respectively, P = 0.002 and 76 versus 66 mmHg, P = 0.01), and tended to have a higher admission systolic BP and pulse pressure (127 versus 121 mmHg, respectively, P = 0.07; and 54 versus 46 mmHg, P = 0.06). The first BP measurement on the 24-hour ABPM was significantly higher in the MH group 140 versus 121 mmHg, P = 0.001, for systolic BP and 84 versus 74 mmHg, P = 0.03, for diastolic BP. Conclusions: MH was found in patients with documented and medically treated vascular disease. BP in the prehypertensive range is associated with MH. Systematic screening for MH in this high-risk population requires further investigation.