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Background: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications., Methods: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426., Findings: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups., Interpretation: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension., Funding: ReCor Medical., Competing Interests: Declaration of interests MA has received research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 programme; has received grant support and non-financial support from ReCor Medical and Idorsia; and has received personal fees from CVRx, AstraZeneca, Alnylam Pharmaceutical, and Poxel Pharma. KS has received grant support and personal fees from ReCor Medical and Medtronic, and has received grant support from Cardiovascular Systems. MSax has received grant support and personal fees from ReCor Medical. PG has received grant support from the University Hospital of Bordeaux. LCR has received personal fees from ReCor Medical. APe has received personal fees from Quantum Genomics and grant support from Ablative Solutions, Quantum Genomics, and ReCor Medical. JB has received grant support from ReCor Medical and Ablative Solutions. MJB has received personal fees from ReCor Medical and Medtronic. JD has received grant support from ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Acist Medical, AstraZeneca, Pie Medical, and Pulse Cath, and personal fees from ReCor Medical, Medtronic, Acist Medical, Boston Scientific, Pie Medical, and Pulse Cath. MDL has received personal fees from ReCor Medical, Medtronic, CVRx, Ablative Solutions, Vascular Dynamics, ROX Medical, and Tarilan Laser Technologies, and grants from Medtronic. FM is supported by Deutsche Gesellschaft für Kardiologie and Deutsche Forschungsgemeinschaft (SFB TRR 219); and has received grant support and personal fees from ReCor Medical, Medtronic, Berlin Chemie, Bayer, and Boehringer Ingelheim. RES has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. ASPS has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Philips. MAW has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Ablative Solutions. APa has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. DH reports institutional funding to Stamford Hospital from ReCor Medical. SB has received grant support from Abbott Vascular, the National Heart, Lung, and Blood Institute, and REATA; and personal fees from Abbott Vascular, Biotronik, REATA, Amgen, Pfizer, Boehringer Ingelheim, and Meril. JW has received personal fees from ReCor Medical and Medtronic. NCB is an employee of ReCor Medical and is the author on multiple patents in the field of renal denervation. HR-S is an employee of ReCor Medical. LC is an employee of ReCor Medical. CKM is an employee of North American Science Associates and a contractor for ReCor Medical. AJK reports institutional funding (in addition to research grants, institutional funding includes fees paid for speaking engagements or consulting) to Columbia University or the Cardiovascular Research Foundation (New York, NY, USA) from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, and ReCor Medical. AJK also reports travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, Chiesi, OpSens, Zoll, Regeneron, and ReCor Medical. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months., Background: The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported., Methods: Patients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety., Results: Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was -2.3 mm Hg (95% confidence interval [CI]: -5.9 to 1.3 mm Hg; p = 0.201) for dASBP, -6.3 mm Hg (95% CI: -11.1 to -1.5 mm Hg; p = 0.010) for office SBP, and -3.4 mm Hg (95% CI: -6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography., Conclusions: Despite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham., Competing Interests: Author Disclosures This work was supported by ReCor Medical. Dr. Azizi has received research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 program; has received grant support and nonfinancial support from ReCor Medical and Idorsia; and has received personal fees from CVRx. Dr. Daemen has received grant support from ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Acist Medical, AstraZeneca, Pie Medical, and Pulse Cath; and has received personal fees from ReCor Medical, Medtronic, Acist Medical, Boston Scientific, Pie Medical, and Pulse Cath. Dr. Lobo has received personal fees from ReCor Medical, Medtronic, CVRx, Ablative Solutions, Vascular Dynamics, ROX Medical, and Tarilan Laser Technologies; and has received grants from Medtronic. Dr. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Hochdruckliga, and Deutsche Forschungsgemeinschaft (SFB TRR 219); and has received grant support and personal fees from ReCor Medical, Medtronic, Berlin Chemie, Bayer, and Boehringer Ingelheim. Dr. Sharp has received personal fees from ReCor Medical, Medtronic, and Philips. Dr. Schmieder has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. Dr. Saxena has received grant support and personal fees from ReCor Medical. Dr. Lurz has received grant support and personal fees from ReCor Medical, Edwards Lifesciences, and Abbott; and has received personal fees from Medtronic and Occlutech. Dr. Bloch has received personal fees from ReCor Medical and Medtronic. Dr. Basile has received grant support from ReCor Medical and Ablative Solutions. Dr. Weber has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Ablative Solutions. Dr. Rump has received personal fees and other support from ReCor Medical. Dr. Sanghvi has received grant support and personal fees from ReCor Medical and Medtronic; and has received grant support from CSI. Dr. Rader has received other support from ReCor Medical. Dr. Fisher has received grant support and personal fees from ReCor Medical. Dr. Gosse has received grant support from the University Hospital of Bordeaux. Ms. Claude is an employee of ReCor Medical. Dr. Barman is an employee of ReCor Medical; and holds multiple patents in renal denervation. Dr. McClure is an employee of NAMSA, a contractor for ReCor Medical. Dr. Kirtane has received institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, Philips, and ReCor Medical; and has received personal fees for continuing medical education, conference honoraria, and travel and meals only. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Pheochromocytoma is a rare disease, which may manifest as severe cardiac complications. Apart from these situations, the "chronic" cardiac impact is not clearly defined. A cardiac MRI study suggests that these patients are carrying areas of fibrosis and foci of left ventricular myocarditis. Since these abnormalities are usually associated with altered left ventricular longitudinal systolic strain, we hypothesize that this strain is altered in patients with a "chronic" pheochromocytoma., Method: This retrospective case-control study was performed using patients from the Bordeaux University Hospital database, included between 2008 and 2016. We compared the left ventricular global longitudinal strain (GLS), radial and circumferential systolic strain and classic echocardiographic parameters between patients with pheochromocytoma and controls matched for age, sex, body mass index and systolic blood pressure., Results: The analysis included 47 patients and 47 correctly matched controls. There were no statistically significant differences between the 2 groups in terms of GLS (-20.7±2.4% vs. -20.2±2.7%, P=0.40), radial strain, left ventricular mass or diastolic function. Left ventricular ejection fraction and circumferential strain were significantly higher in patients than in controls, with a significantly lower telediastolic diameter., Conclusion: No significant changes in GLS were observed in our pheochromocytoma patients, compared with controls. Several hypotheses may explain these results. The presence of fibrosis foci and areas of left ventricular myocarditis being associated with a poor cardiological prognosis, a systematic cardiac MRI could be discussed in these patients, until further studies are performed., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: Primary hyperaldosteronism is the leading cause of secondary hypertension, and leads to frequent cardiovascular complications. Many studies have studied left ventricular geometry and function in this population, but longitudinal systolic function is still poorly described., Methods: We studied 35 hypertensive patients with primary aldosteronism, and 35 with essential hypertension matched for age, sex, body mass index, and 24h blood pressure. Patients benefited from an echocardiography to measure the mass and the geometry of the left ventricle, left ventricle ejection fraction, systolic longitudinal, circumferential, and radial strain, and diastolic function., Results: Compared to essential hypertensive patients, patients with primary aldosteronism presented a significantly higher left ventricular mass index and relative wall thickness (60.3±16.1g/m 2 vs 47.3±18.6, P=0.003, and 0.44±0.08 vs 0.36±0.06, P=0.00005, respectively), as well as a significantly reduced longitudinal systolic strain (-17.8±3,4 vs -20.3±3,6%, P=0.004). There were no significant differences in the other parameters., Conclusions: Primary aldosteronism is associated with a deterioration of longitudinal systolic function of the left ventricle compared with essential hypertensive patients. This marker of cardiac damage, reproducible and easily available in routine could help for the screening of these patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Depending on the study, the prevalence of primary aldosteronism (PA) in patients with hypertension varies from 6 to 18%. Prevalence is higher in each of the following conditions, any one of which requires screening for PA: severe hypertension (systolic blood pressure [BP]≥180mmHg and/or diastolic BP≥110mmHg); resistant hypertension (systolic BP≥140mmHg and/or diastolic BP≥90mmHg despite adherence to a tritherapy including a thiazide diuretic); hypertension associated with hypokalemia (either spontaneous or associated with a diuretic); Hypertension or hypokalemia associated with adrenal incidentaloma. It should be borne in mind that PA can induce hypertension without hypokalemia or, less frequently, hypokalemia without hypertension. Finally, as cardiovascular and renal morbidity in PA is greater than in essential hypertension of equivalent level, screening for PA is indicated when cardiovascular or renal morbidity is more severe than predicted from BP level., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Impairment of the autonomic nervous system activity may be involved in the development of hypertension. Yet the prognostic values of heart rate variability and baroreflex sensitivity in the risk of new-onset ambulatory hypertension have not been investigated. We sought to assess the relationship between heart rate variability and baroreflex sensitivity parameters and ambulatory hypertension in a community-dwelling elderly cohort., Methods: Normotensive subjects were selected from the PROOF study cohort, including 1011 subjects aged 65 years at baseline. The autonomic nervous system activity was assessed through 24-hour heart rate variability and 15-minute spontaneous baroreflex sensitivity at baseline. Incident hypertension was defined with the 24-hour, day-time and night-time ambulatory blood pressure measurements and antihypertensive treatment use, at two-years of follow-up., Results: At baseline, 13.7% of subjects developed day-time hypertension, 18.2% developed night-time hypertension and 13.6% developed 24-hour hypertension. Reduced baroreflex sensitivity at baseline was associated with onset of hypertension after adjustment for blood pressure level, C-reactive protein levels and depression score (OR = 0.45 [0.23-0.86]). Indices of heart rate variability were not associated with hypertension onset., Conclusion: Baroreflex sensitivity may represent an intermediate goal for prevention of ambulatory hypertension at early stage., (© 2013.)

Background: Sympathetic "overactivity" during night is a well recognized factor of hypertension development in adults. However, the deleterious effect of nocturnal autonomic activation in elderly remains controversial., Methods: Subjects, all aged 65 years at baseline, were selected from the PROOF cohort study, a prospective observational cohort of subjects. Exclusion criteria were previous myocardial infarction, stroke, heart failure, type-1 diabetes, atrial fibrillation or anti-arrhythmic drug. Normotensive subjects were selected according to: 24-h ambulatory blood pressure (BP) measurements <135/85 mm Hg, absence of self-report antihypertensive treatment. Autonomic activation during sleep was evaluated from night-time ECG Holter recording. According the %VLFI (Very-Low Frequency component of Interbeat Interval Increment evaluated from heart rate variability analysis). Subjects with new-onset ambulatory hypertension were identified after two years when daytime ambulatory blood pressure was higher than 135/85 mm Hg or when they used an antihypertensive treatment., Results: Among 428 normotensive subjects at inclusion, 62 (14.5%) were considered as hypertensives after two years. Univariate logistic regression model showed a significant association between abnormal %VLFI (>4%) and new-onset hypertension: OR = 1.78 (1.03-3.07). Male gender, increased body mass index and ambulatory systolic BP were also associated with increased risk of hypertension. After adjustment in the stepwise logistic regression, abnormal %VLFI was associated with an 82% increase in odds of new-onset hypertension, independently of systolic ABPM and body mass index., Conclusion: Repeated autonomic activation during sleep, whatever the origin of the phenomenon, may trigger hypertension development in the elderly., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To compare clinical, vascular and metabolic parameters before and after surgery in patients with subclinical cortisol secreting incidentalomas., Patients and Methods: Eight patients were investigated before and 12 months after removal of the mass on hemodynamic (blood pressure by MAPA procedure), anthropometric (body weight, body mass index), and metabolic parameters (glucose level, HbA(1c))., Results: In the whole group, 75% of patients displayed decrease in blood pressure (cessation of at least one hypotensive medication) and 33% of them were definitely cured of hypertension. Seventy-one percent of patients lost body weight and 37.5% lost more than 5%. In the whole group of patients, glucose level decreased by 1.1% and medical treatment was discontinuated in two of three diabetic patients., Conclusion: Subclinical cortisol secreting adrenal incidentalomas are associated with cardiovascular risk factors that may be corrected after removal of the mass. Therefore, surgery may be an appropriate choice in patients with subclinical Cushing's syndrome to improve hypertension, body weight and impaired glucose level. Controlled studies comparing surgical treatment to a medical follow-up including optimal cardiovascular risk factors treatment are needed to define the usefulness of surgery in hypertensive patients with subclinical cortisol secreting incidentalomas.

Background: Laparoscopic surgery for phaeochromocytoma can cause excessive catechol amine release with severe hypertension and sinus tachycardia. i.v. calcium antagonists may be used to prevent increases in blood pressure during phaeochromocytoma resection. We investigated the effects of perioperative alpha(1) adrenergic block with urapidil on intraoperative haemodynamic events. The aim was to block the alpha(1) adrenergic receptors before any acute catecholamine release, to prevent any severe rise in blood pressure., Methods: Eighteen patients with a phaeochromocytoma received a continuous i.v. infusion of urapidil 10-15 mg h(-1) for 3 days before surgery and until the adrenal gland had been removed. Plasma catecholamine concentrations were measured before surgery, after induction of anaesthesia, at the end of pneumoperitoneal insufflation, during gland manipulation, after gland resection, and in the recovery room after extubation. Arterial pressure was recorded concomitantly. Hypertensive events were treated with boluses of nicardipine with or without esmolol., Results: All patients had the adrenal tumour removed without any severe rise in blood pressure or other complication. Creation of a pneumoperitoneum and adrenal gland manipulation induced significant catecholamine release associated with hypertension in 6 and 12 patients, respectively. No correlation was found between hypertensive events and plasma catecholamine levels suggesting alpha(1) receptor block with urapidil is efficacious., Conclusions: Perioperative alpha(1) block using i.v. urapidil is a safe and efficient alternative during surgical management of phaeochromocytoma.

Objective: To investigate the effects of coeliosurgery by catecholamine assays and the use of urapidil in the management of phaeochromocytoma., Study Design: Prospective cohort study., Patients: Nine consecutive patients from April 1997 to April 2001., Methods: Urapidil (250 mg.j-1) was administered by continuous intravenous infusion three days before surgery and continued throughout anaesthesia. Plasma catecholamine concentrations were measured before surgery, after induction of anaesthesia, during insufflation, after adrenalectomy and in the recovery room. Haemodynamic disorders were treated by nicardipine +/- esmolol bolus doses., Results: Creation of pneumoperitoneum and adrenal gland manipulations resulted in significant catecholamine releases associated with hypertension in five and eight patients respectively. Preventive urapidil use enabled easy control of blood pressure variations by additive antihypertensive drugs., Conclusion: Perioperative alpha 1 blockade by urapidil enables an effective and easy control of acute preoperative haemodynamic changes.

Introduction: Distensibility is the ability of large elastic arteries to increase in diameter from diastole to systole. Pulse wave velocity (PWV) is one of the ways to measure this parameter. Several techniques, including QKd, are able to measure PWV., Purpose: QKd is the time interval between the Q wave on EKG and auscultation of the second Korotkoff's sound at the brachial artery. QKd is measured by a specific apparatus that registers ambulatory blood pressure as well as EKG (normal > 200 ms). Arterial distensibility seems to be able to predict cardiovascular morbidity and QKd has been demonstrated to predict such morbidity in a sample of elderly hypertensives. Currently the relationship between QKd and prognosis is under investigation in systemic sclerosis (ERAMS study)., Conclusion: QKd is a noninvasive ambulatory method that measures arterial distensibility as well as blood pressure.

Valsartan, an angiotensin II antagonist with a potent and highly selective effect on AT1 receptors, has been found effective and safe in several randomized, controlled studies versus a placebo, other antihypertensive agents, or other angiotensin II antagonists. An eight-week, open-label, multicenter, prospective, pragmatic, phase IV trial was conducted by office-based cardiologists to evaluate the clinical safety and efficacy of valsartan 80 mg in everyday practice. The efficacy analysis included 3084 patients given valsartan alone for four weeks then, during the next four weeks, either valsartan alone or, if the diastolic blood pressure was still > or = 90 mmHg, valsartan in combination with another antihypertensive agent. The valsartan dosage was 80 mg/day. On day 28, 64% of patients were controlled and 78% were responders. The safety analysis included 3,108 patients. Of the 239 medical adverse events ascribed by the investigators to the study treatment, 72 led to premature study discontinuation. This figure translated into a 2.68% rate among treated patients, which is similar to the 2.3% rate recorded during the placebo-controlled trials performed as part of the valsartan clinical development program. These results confirm the outstanding safety profile of valsartan.

When a correlation between an individual characteristic and the incidence of a disease is detected in epidemiology, this characteristic must satisfy four criteria before it can be considered to be a risk factor it must be strongly associated, universally associated regardless of the population, gender, race, associated independently of already recognized factors, especially age, and a cause-and-effect relationship must be demonstrated by a study influencing this characteristic. The first three criteria define the risk marker. Various examples are given, including that of heart rate and overall and cardiovascular morbidity and mortality.

The artery is subject to tangential mechanical forces, involving heart rate and shearing forces. A mechanical theory of atherosclerosis explains the preferential development of plaques according to the distribution of these forces. Experimental data and an epidemiological article are in favour of the role of heart rate in cardiovascular complications. However, the benefit of therapeutic reduction of heart rate will probably be difficult to prove except in cases in which arterial lesions develop rapidly, as demonstrated in Marfan's disease.

With the exception of cardiac surgery, the acute disturbance of the left ventricular diastole occurs mainly in the elderly. Today it represents 30 to 40% of congestive cardiac failures, however with a lower mortality than for acute systolic disturbances. Generally indicated are relaxation anomalies, proto-mesodiastolic mechanism and problems with compliance, an indicator of the pressure/volume diastolic relationship. Invasive techniques remain the standard method. Doppler echocardiography is becoming increasingly important for the assessment of diastolic function. In most cardiopathies, relaxation anomalies occur early, whereas compliance disturbances are mainly associated with advanced cardiac diseases. During anaesthesia, adverse events (auricular fibrillation, hypovolaemia) may worsen a fragile situation. Anaesthetic agents, in particular volatile agents, act on the ventricular diastole. Long-term therapy of diastolic anomalies includes agents amending left ventricular hypertrophy. Emergency therapy has not yet been systematised.

The efficacy and safety of trandolapril alone and in combination with a calcium channel blocker were evaluated in 13,147 hypertensive patients over 60 years old. Two patient groups were constituted. After a 2-week wash-out period, the patients in group I received monotherapy with trandolapril 2 mg/day for 4 weeks. Trandolapril was continued for another 4 weeks in responding patient, otherwise the dosage of trandolapril was doubled or another antihypertensive was added. Group 2, composed of patients previously treated with a calcium channel blocker with insufficient efficacy, was treated according to the same treatment regimen, but the calcium channel blocker was maintained throughout the study. 13,147 patients (group 1: 11,329 patients, group 2: 1,818 patients) with a mean age of 68 +/- 7 years were followed. After 4 weeks of treatment, the blood pressure measured by mercury sphygmomanometer decreased from 176 + 11/99 +/- 8 mmHg to 164 +/- 12/87 +/- 7 mmHg (p < 0.0001). This blood pressure fall was similar in group 1 (-22 +/- 12/-12 +/- 8 mmHg) and in group 2 (-21 +/- 11/-12 +/- 8 mmHg). In the pure systolic HT subgroup treated by trandolapril monotherapy, the antihypertensive effect predominantly affected the SBP (-23 +/- 12/- 4 +/- 6 mmHg). The antihypertensive effect was correlated with the initial blood pressure. In group 1, in the case of insufficient response to trandolapril monotherapy, the addition of a calcium channel blocker was the strategy which achieved the most marked antihypertensive effect (ANOVA, p < 0.0001). This bitherapy was more effective than the trandolapril+diuretic combination (-18 +/- 11/- 11 +/- 8 mmHg and -15 +/- 10/- 9 +/- 7 mmHg, respectively (p < 0.001). A total of 1,270 adverse events were reported by 996 patients (7.6%), leading to discontinuation of treatment in 372 patients (2.8%). The most frequent adverse effects were cough (2.8%), headache (0.8%), vertigo (0.8%) and nausea (0.5%). Only one minor equivalent of angioneurotic oedema was reported. In conclusion, trandolapril is effective and well tolerated in elderly hypertensive patients. In the case of pure systolic HTA, its action is essentially exerted on SBP. The combination of trandolapril+calcium channel blocker appears to be the most effective strategy in the case of incomplete blood pressure control by trandolapril alone.

The increasingly frequent use of arteriography in the investigation of hypertension and of obliterative arterial disease of the lower limbs has led to recognition of the actual incidence of renal artery aneurysms. The importance of this type of lesion is due to the fact that the natural history of renal artery aneurysms remains unknown, their relationship with hypertension is still controversial and the risk of complications, and rupture in particular, has led to the suggested possible need for their routine surgical excision. The current trend is to limit indications for surgery to certain specific cases since a number of recent series have shown that the risk of rupture of a small saccular aneurysm was very small.

Familial cases of lupus anticoagulant were rarely described. We report the observation of two sisters with lupus anticoagulant, one with thrombocytopenic purpura and the other with systemic lupus erythematosus.

Echo-duplex exploration of heart and inferior limbs arteries is performed in 76 patients less than 60 years old, with angiographically established coronary heart disease. Peripheral vascular lesions are found in 15 cases (20%), they are more frequent in patients with tritrunkular coronary disease (35%) than in those with one (16%) or two-vessel lesions (10%). Mean encephalic circulatory resistance index is higher in patients with tritrunkular lesions (p less than 0.03). Vascular echo-duplex should be performed in case of coronary disease in order to avoid catheterism complications and to purpose combined surgical procedure (coronary bypass and carotid endarterectomy).

The aim of this study is to specify the feasibility and value of the diameter measurement of the jet of aortic insufficiency (AI) in colour Doppler. 68 consecutive patients had a supra-sigmoid angiography and a colour echo-Doppler. An aortic insufficiency was revealed 58 times by the angiography and Doppler. In all the cases except four, it has been possible to measure the jet diameter at the origin in para-sternal incidence in colour TM by confronting the images in great and small axis section. The Doppler results have been compared to the angiographic score in 4 grades according to Sellers classification. The jet diameter at the origin in colour TM is significantly different in groups I, II, III-IV. In the group III-IV, it is always higher or equal to 13 mm. The failures of quantification of the AI jet in colour Doppler are linked with the very eccentric nature of the jet or to the poor quality of the echo-Doppler imaging. On the whole, the jet diameter measurement proves to be a very useful element in the assessment of the gravity of an AI, particularly when it is a central and circular jet.

Chronic aortic insufficiency is, since a few years, a topic of renewed interest because of the development of non-invasive monitoring methods: sonocardiography, cardiac Doppler. The problem raised is that of deciding the most opportune time for surgery in asymptomatic chronic AI, the course of which may quietly evolve towards irreversible myocardial lesions. The severity of AI may be determined by numerous sonocardiographic and Doppler criteria. In sonocardiography, three types of parameters have especially been studied: ventricular expansion (telediastolic, telesystolic diameter), the systolic function (percentage of diameter decrease), volume/mass ratio (R/h). To be valid, these measurements are a precious guide for patient's monitoring and therapeutic approach. The more recent Doppler criteria must be validated on large series and evaluated according to the context or a pathological association; they all have limitations and cannot be interpreted separately.

Antihypertensive therapy has markedly improved, in the last few years, but, in some patients, the blood pressure remains high despite an association of several medications. We are proposing to consider as persistent or refractory, any essential hypertension remaining higher than or equal to 165/95 despite a well administered triple therapy, initiated since at least one month. With such patients, the first step consists in verifying the various terms of the definition: measurement of the blood pressure under standard condition and, at best, over a long period of time, in ambulatory conditions; re-evaluation of the drug combination (synergistic action); observance of the treatment by the patient; re-investigation of the etiology; determination of the resistance factors to the treatment. The treatment should then be patiently and methodically reviewed, based on the most potentialized combinations, taking into consideration the first signs of occurrence of the hypertension, without neglecting hygieno-dietetic measures. Sometimes, it will be necessary to resort to more potent treatments, which are more delicate to handle.

The knowledge of the characteristics and consequences of left ventricular hypertrophy (LVH) in the hypertensive patient has greatly progressed in the past few years, owing to echocardiography. This examination provides a reliable and reproducible measurement, and therefore the left ventricular mass is used more and more as a severity index of hypertension and a mean of evaluation of the efficacy of the treatment. This attitude is justified in part by the poor prognosis of LVH. However, the pathogenesis of LVH in hypertension still presents numerous unknown facts. If the elevation of the post-charge seems to be the essential mechanism, other factors seem to have an important influence and explain the uneven effect of different hypertensive drugs at this level. Presently, there are several arguments in favor of the beneficial character of the regression of LVH in the hypertensive patient under treatment, but we will have to wait for the result of prognostic studies to use this property as a major objective of anti-hypertensive treatments.

Since arterial hypertension is one the main risk factors of coronary atherosclerosis, the association hypertension-coronary disease is a frequent one. Moreover, arterial hypertension aggravates the coronary disease and this association is therefore of very poor prognosis. However, this prognosis seems to improve with early and adapted treatment based largely at this time on beta-blockers and calcium inhibitors.

When facing a chronic hypotension, underlying chronic diseases must be ruled out. In most cases, it concerns a "constitutional" benign, low blood pressure, however ill-tolerated and associated with neurovegetative dystonia. In so far as it is not a disease, there is no specific treatment. The long-term prognosis is excellent since symptoms usually improve with years and a low blood pressure is a sign of longevity.

Ultrasound provides anatomical (wall thickness, diameter) and functional (thickening of the wall, ventricular ejection, ventricular filling) information about the left ventricle. The reliability and reproducibility of these measurements have been improved by the development of mono and bidimensional techniques, so that, today, ultrasound is the method of choice for the investigation and surveillance of left ventricular function, provided it is of good quality. Apart from the indirect information about left ventricular function drawn from mitral or aortic traces, the echocardiogram has proven to be a reproducible method for estimation of the thickness of the ventricular wall, the ventricular diameters and the left ventricular muscle mass. Whatever the geometry of the left ventricle, the ventricular volume is assessed most accurately by bidimensional ultrasound.

Although infrequent, acute aortic insufficiency must be identified at an early stage. The clinical picture is often deceptive. Ultrasonic cardiography and cardiac Doppler represent, today, a diagnostic technique of choice which specify the mechanism of the acute valve leakage, the condition of the ascending aorta and the repercussions on the left ventricle.