[The optimal work-up before TAVI]. / Le bilan optimal avant TAVI.

The number of TAVI procedures is rapidly increasing owing to the extension of indications. Procedural and long-term success warrant appropriate patient selection and rigorous preparation of the procedure during the pre-TAVI work-up. The aims of this work-up are several: validation of the indication, feasibility and safety of the procedure, selection of the prosthesis and of the route, anticipation of technical challenges. The CT-scan is the cornerstone of this assessment allowing for valve and vascular access appraisal. The geriatric evaluation remains important in the elderly, frail, high-risk patients. The assessment of cardiac and extracardiac comorbidities is systematic and may be incorporated into dedicated risk scores to improve the prediction of post-TAVI outcomes; this should be the basis of the decision-making process by the Heart Team.

Position paper of French Interventional Group (GACI) for TAVI in France in 2018.

Aortic stenosis is a frequent disease in the elderly. Its prevalence is 0.4% with a sharp increase after the age of 65, and its outcome is very poor when the patient becomes symptomatic. The interventional procedure known as TAVI (trans-catheter aortic valve implantation), which was developed in France and carried out for the first time in Rouen by Prof. Alain Cribier and his team in 2002, has proven to be a valid alternative to surgical aortic valve replacement. At first, this technique was shown to be efficient in patients with contra-indications to surgical treatment or deemed to be at high surgical risk. Given the very promising outcomes achieved as a result of close heart team collaboration, appropriate patient selection, simplified procedures and reduced complication rates, transfemoral (TF) TAVI is now preferred in symptomatic intermediate risk patients>75 years old according to the latest ESC guidelines. In 2017, in France, TAVI is currently performed in 50 centers with on-site cardiac surgery. The 2016 TAVI outcomes recorded in the French national TAVI registry (France TAVI) are very encouraging and show that for 7133 patients treated (age 83.4±7 years, logistic Euroscore 14%), 87% of whom via the TF approach, cross-over to surgery was very low (0.5%) with a 3.0% in-hospital mortality rate. The substantial increase in TAVI indications and the improvement of its outcomes may in the near future call for a reconsideration of the number of high volume centers authorized to carry out this technique.

[Comparison of four formulas of adjusting QT interval for the heart rate in young elite athletes]. / Intervalle QT chez les athlètes : comparaison de quatre formules de correction dans une population de jeunes sportifs de haut niveau.

PURPOSE: Sudden cardiac death in young athlete is always tragic. Some international guidelines recommend the realization of an electrocardiogram before practicing competitive sports to carry out the risk of sudden cardiac death due to genetic cardiopathy like QT long syndrome. Unfortunately, the diagnosis can be difficult because intensive sport can increase the QT interval over normal recognized values for sedentary people. Using a QT correction formula free of heart rate appears essential. PATIENTS AND METHODS: Four hundred and forty-six young athletes (aged 10 to 18) had an electrocardiogram. QT intervals were measured and four methods were used to correct the QT interval for heart rate. RESULTS: The Bazett formula performed the worst in terms of rate adjustment success. Hodges and Fridericia formulas are the best both in males and females, independently of age. Female had longer QTc intervals than males. CONCLUSION: The most widely used Bazett formula should be surrendered whereas Hodges and Fridericia formulas should be preferred, particularly in young athletes.

[Renal denervation for treating hypertension: experience at the University Hospital in Lyon]. / Dénervation rénale dans le traitement de l'hypertension artérielle résistante : expérience du CHU de Lyon.

AIM: We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension. PATIENTS AND METHODS: Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5±11.5 years, BMI 33±5kg/m(2) and ambulatory blood pressure 157±16/87±13mmHg with 4.2±1.5 anti-hypertensive treatment. RESULTS: We did not observe intra-operative or early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20±15 (P<0.001) and 10±13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5±14.9mmHg (P=0.027) for SBP and of 10.5±9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4±3mm (P=0.031), Sokolow index of 3±3mm (P=0.205), Cornell voltage criterion of 9±7mm (P=0.027) and Cornell product of 1310±1104 (P=0.027). CONCLUSION: Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe.

[Athlete's heart in the young: electrocardiographic and echocardiographic patterns in 107 French athletes]. / Le cœur d'athlète de l'adolescent : aspects électrocardiographiques et échocardiographiques. À propos de 107 sportifs français.

PURPOSE: Since 2009 in France, every people practicing sport in competition must have a cardiovascular exam with electrocardiogram, to prevent sudden cardiac death. Sometimes, an echocardiography will be necessary. Little is known about athlete's heart in the young, particularly in the French people. PATIENTS AND METHODS: One hundred and seven French elite adolescent athletes had an electrocardiogram with echocardiography to establish reference values in this population. RESULTS: QTcorrected (QTc) interval calculated by the Hodges formula, is always in the normal values. Interventricular septal thickness is always ≤ 11 mm and left ventricular end diastolic diameter ≤ 55 mm in about 90 % of the athletes. Females have QTc interval longer than males and interventricular septal thickness finer. Diastolic function (18.9 ± 2.6 cm/s for e', E/e' ratio at 5.3 ± 0.8) is "supernormal" and correlate with age and cardiac frequency. Right ventricular systolic function is always good. CONCLUSION: Adolescent athlete's heart is normal. If QTc interval is not normal, be afraid of a QT long syndrome. Furthermore, when interventricular septal thickness is > 11 mm or left ventricular end diastolic diameter > 55 mm, myocardiopathy will have to be ruled out.

[Associated factors for sleep apnea in heart failure]. / Facteurs associés au syndrome d'apnées du sommeil dans l'insuffisance cardiaque.

OBJECTIVE: Genesis of sleep apnoea syndrome (SAS) in chronic heart failure (CHF) is not well known. The aim of our study was to find associated factors to SAS in heart failure (HF) and to look for differences between central sleep apnea (CSA) and obstructive sleep apnea (OSA). PATIENTS AND METHODS: We realised a cross-sectional and retrospective study. Thirty patients with stable heart failure under medical optimal therapy were included. Polygraphy, echocardiography and cardiopulmonary exercise were systematically performed. RESULTS: Men were predominant (80%) in the group. Mean age, left ventricular ejection fraction (LVEF) were respectively 64.1±13.8years and 40±9.8%. SAS was present in 60% of patients (33.3% were classified as central sleep apnoea [CSA] and 26.7% as obstructive sleep apnoea [OSA]). Body mass index, blood pressure and left ventricular pressures estimated by the E/Ea ratio were significantly higher in the group with SAS (P<0.05) compared to the non SAS group. New York Heart Association class was significantly higher (P=0.04) and the predicted peak VO(2) was significantly lower in CSA patients compared to OSA patients. CONCLUSION: High left ventricular pressures estimated by the E/Ea are significantly associated with SAS in heart failure. CSA patients tend to have a worse functional state than OSA patients.

[Diabetes and hypokinetic cardiopathy : when to consider mitochondrial disease?]. / Diabète et cardiopathie hypokinétique, quand évoquer une cytopathie mitochondriale ?

The association between diabetes mellitus and hypokinetic cardiomyopathy is frequent. We report a case of diabetes and hypokinetic cardiopathy in a 40-year-old man which led to the hypothesis of maternally inherited diabetes and deafness (MIDD) due to a mitochondrial disease. This diagnosis was confirmed by genetic testing which showed a DNA A3243G mutation in the mitochondria, the prevalence of which is 1-2% in diabetes mellitus. Cardiac abnormalities are frequent (18-34% of patients depending on the series) and the co-existence of left ventricular hypertrophy and systolic dysfunction is suggestive of this disease. Some authors have proposed co-enzyme Q as a treatment to improve the left ventricular ejection fraction and insulin secretion.

Persistent left superior vena cava with absent right superior vena cava: a difficult cardiac pacemaker implantation.

An absent right superior vena cava associated with a persistent left superior vena cava (PLSVC) is a rare and generally asymptomatic congenital malformation. It is usually discovered incidentally during a pacemaker (PM) implantation. We report here a successful PM implantation using a left subclavian approach through the coronari sinus via a PLSVC, with a 2-year follow-up showing a still appropriate function of the device. We discuss the clinical usefulness of peripheral phlebography in the operating room for delineating precisely the venous anatomy, as well as the role of shaped stylets and active fixation leads to overcome technical difficulties.

Diagnosis of an uncommon case of myocarditis by cardiac magnetic resonance imaging: ventricular tachycardia caused by inflammatory left ventricular microaneurysms.

Cardiac magnetic resonance imaging (CMRI) has recently proved to be a powerful tool in the diagnosis of myocarditis. We report a case of myocarditis diagnosed with CMRI in a rare setting: An episode of ventricular tachycardia (VT) arising from the left ventricle associated with a unique ventricular microaneurysm in a patient free of coronary disease. Because of this benign feature, the patient was discharged with antiarrhythmics with no further investigation. A 9-month follow-up revealed no VT recurrence. This case demonstrates the importance of CMRI in patients suffering from apparently idiopathic VT originating in the left ventricle.

Arterial stiffness is associated with left atrial size in hypertensive patients.

BACKGROUND: Arterial stiffness is a strong predictor of cardiovascular events and particularly of stroke. A likely explanation is the development of atherosclerotic lesions at the carotid level, favored by increased local stiffness. Another possibility involves cardiac consequences of aortic stiffness and particularly left atrial dilatation with its subsequent risk of atrial fibrillation (AF) and cerebral embolism. AIMS: The present study investigated the link between arterial stiffness, pulse pressure and left atrial size, a determinant of AF risk. METHODS: Arterial stiffness was determined from pulse wave velocity (PWV) and pulse pressure (PP). Left atrial size was also measured. Several potential confounders were taken into account including indices of ventricular remodeling and diastolic function (estimated by NT-Pro brain natriuretic peptide (NT-proBNP) levels). RESULTS: Three-hundred and ten hypertensive patients, aged 53 +/- 13 years, were included. Mean 24-h blood pressure (BP) was 154 +/- 20 over 93 +/- 13 mmHg. Significant relationships were found between left atrial diameter (LAD) and PWV (r=0.27, P<0.001) and between LAD and 24-h PP (r=0.32, P<0.001). LAD was also correlated significantly, although not always tightly, with left ventricular dimensions, geometry and NT-proBNP. In two different multivariate models, LAD remained significantly correlated with PWV or with 24-h PP, independently of classical determinants like age, gender, body mass index, ventricular remodeling (i.e. dimensions and geometry) and filling pressure. CONCLUSION: These results led us to propose AF as a new possible pathophysiological link between arterial stiffness and stroke. These results also emphasize the cardiac consequences of arterial stiffness which can fuel a new approach to AF prevention.

[Markers of cardiovascular remodeling in hypertension]. / Marqueurs du remodelage cardiovascularire structural et fonctionnel dans l'hypertension.

UNLABELLED: Our goal was to study the relative influence of systolic blood pressure (SBP) and plasmatic markers of sympathetic and renin-aldosterone systems (RAS) activities to left atrial diameter (LAD), left ventricular posterior wall thickness (LVPWT) and pulse wave velocity (PWV), which reflect cardiovascular remodeling in hypertension. METHODS: In 227 consecutive patients with hypertension (mean age +/- SD: 53.3 years +/- 13.4, 126 men), we measured: PWV, LAD, LVPWT, mean 24-hours SBP, plasma renin activity, and plasma aldosterone and catecholamine levels. Multiples linear regression analyses were performed to test statistical associations between hemodynamic and neurohumoral factors, and cardiovascular remodeling parameters, after adjustment for age, gender and body mass index. RESULTS: LVPWT was positively correlated to SBP as well as to plasma aldosterone and meta-noradrenaline (p < 0.001). LAD and PWV were related to SBP but not to any of the biological variables. Moreover, LAD correlated to PWV independently of SBP (p < 0.05), whereas after SBP inclusion in the model, there was not significant correlation between LAD and LVPWT nor between LVPWT and PWV. CONCLUSION: In hypertension, the development of cardiac hypertrophy depends on SBP and the sympathetic and renin-aldosterone systems activities. The RAS is not involved in the PWV nor LAD modifications. Strong association between LAD and PWV suggest that left atrial enlargement, that may be considered as a marker of diastolic function, may results more from arterial stiffness than from ventricular hypertrophy.

[Medical stress and blood pressure]. / Stress médical et pression artérielle.

BP measurement by a physician may trigger a blood pressure and heart rate increase often referred to as the white coat effect. This pressure response may occur both in normotensive and hypertensive subjects. The identification of such individuals is usually not possible on a clinical basis. This identification is however important because white coat effect and permanent hypertension do not share the same prognosis, the white coat effect being associated with a low rate of cardiovascular complications. To avoid an important overestimation of the real blood pressure level due to this white coat effect, it is possible to increase the delay before blood pressure measurements (beyond 15 minutes) or to take into account measurements made by nurses. Reading may also have a favorable consequence. However, a blood pressure recording outside the office, that is an ambulatory or a home blood pressure measurement, is the only way to confirm the presence of a white coat effect. The decision to treat is based on this measurement.

[Clinical implications of blood pressure variability]. / Implications cliniques de la variabilité tensionnelle.

There are many variations in blood pressure, ranging from that observed between systole and diastole (pulse pressure) to slower daily or seasonal variations. This variability has many facets, for example the simple concept of variation around the mean blood pressure and the more complex spectral, chaos or fractal analysis... Some of these concepts are still the subject of fundamental research and have no current clinical applications. Others, however, are already part of our evaluation of hypertensive patients or used as prognostic factors in cardiac failure or myocardial infarction. Blood pressure variability, either the pulse pressure or 24 hour variability, is associated with a higher incidence of cardiovascular complications. Although the causality of the relationship is uncertain, patients with the greatest variability seem to be at higher risk. In addition to this prognostic impact, the study of changes in blood pressure by spectral analysis may also provide indices of adrenergic tone or sympathovagal equilibrium which may be useful clinically. Finally, the combined study of blood pressure variability and heart rate lead to the baroreflex, the sensitivity of which integrates major risk factors such as blood pressure, age, heart rate and serum cholesterol. This baroreflex could be a useful parameter for stratification of cardiovascular risk. This has already been demonstrated in patients at high risk, such as those with cardiac failure or myocardial infarction.

[Adrenal vein catheterization in primary hyperaldosteronism: aid in surgical decision making?]. / Cathétérisme des veines surrénales dans l'hyperaldostéronisme primaire: aide à la décision chirurgicale?

UNLABELLED: The localisation of aldosterone-producing adenomas (APA's) remains difficult. Indeed, CT scan may not detect small APA's while CT detected tumours do not necessarily produce aldosterone. OBJECTIVE: To evaluate the value of adrenal vein catheterization (AVC) for the diagnosis of APA's and also the rates of unsuccessful procedures and complications. PATIENTS: One-hundred-and-nine hypertensives with biological features of primary hyperaldosteronism were included. Plasma sodium, potassium, aldosterone and renin levels were obtained after one night in lying position. Aldosterone and renin levels were also measured after a one-hour walking period and after a sodium expansion with saline. All patients underwent a CT scan and AVC. For adrenal samples, the ratio of aldosterone to cortisol concentrations was calculated for both sides. Both ratios were divided by the opposite one and the higher was retained as an index of laterization (IL). For lack of a golden standard variable, we have taken as a working hypothesis that operated patients had an APA (n = 38) and the non operated ones bilateral hypereplasia (n = 71). RESULTS: Operated patients had a shorter history of hypertension, more frequently a left ventricular hypertrophy on ECG, and lower serum creatinine and potassium levels, along with a higher sodium level. None of these features appeared discriminant, however. Presence of a 10-mm tumour on CT scan was not significantly different between the 2 groups. Operated patients had more than a five-fold higher IL compared with that of non-operated patients. Analysis using a ROC curve showed that the value of 12 for "IL" was an acceptable operational criterium of lateralization, producing a specificity of 90%, while maintaining a sensitivity of 62%. AVC appeared most useful in case of middle-range pre-test probability of an APA being present, that is when when clinical, biological, or radiological features are not fully concordant. The rate of unsuccessful procedure and the rate of complications were low (1.8% and 3.6%, respectively). CONCLUSION: With a low iatrogenicity, AVC appears helpful in indicating surgery mostly when clinical, biological, and CT scan features are not fully concordant. A value of 12 for IL appears to allow a high specificity while retaining an acceptable sensitivity.

[The best in 2000 on arterial hypertension]. / L'essentiel de 2000 en hypertension artérielle.

The authors showed, in a spin-off study of SYST-EUR, that 24% of subjects with isolated systolic hypertension on conventional measurement were not hypertensive during ambulatory blood pressure monitoring. Moreover, in white coat hypertension, treatment had no effect either on the electrical signs of left ventricular hypertrophy or on the incidence of clinical events (cerebrovascular accident and global cardiovascular complications), contrary to what is observed in permanent systolic hypertension. These results raise question as to the diagnosis and treatment of isolated systolic hypertension in the elderly and prompt to a larger usage (if not systematic) of ambulatory blood pressure monitoring in this context. The importance of systolic blood pressure and pulsed pressure For different reasons, diastolic blood pressure was thought to be of greater prognostic significance, as the very large majority of clinical trials recruited on the basis of the value of their diastolic blood pressure alone demonstrate. In recent years, the importance of systolic blood pressure has been underlined in many studies and 3 trials have shown the unquestionable benefits of treatment of isolated hypertension. It would also appear that the pulse pressure, which reflects arterial compliance, has considerable prognostic value. In the absence of established manometric criteria and mostly of therapeutic trials, the practical use of the pulse pressure remains questionable. The interruption of the doxazosin arm of the ALLHAT trial The ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) study showed a doubling of the morbidity from cardiac failure, a 19% excess of cerebrovascular events and 16% of angina pectoris in subjects treated with doxazosin compared with those treated with chlorthalidone. The differences in blood pressure with treatment were minimal and, a priori, unable to explain these results. Beyond the fact that alphablockers cannot be considered as first-line antihypertensive therapy, without doubt, the affirmation that lowering the blood pressure provides the same benefit irrespective of the antihypertensive agent used, probably needs to be reviewed.

[Primary prevention of coronary thrombosis by antithrombotic agents]. / Prévention primaire de la thrombose coronaire par les antithrombotiques.

At the start of the eighties, in the wake of the good results obtained with aspirin in secondary prevention, two studies were launched aimed at testing the effect of aspirin on the primary prevention of myocardial infarction. The results published in 1988 and 1989 were divergent: the study conducted by British doctors showed no benefit with aspirin, that conducted by American doctors showed a very distinct benefit concerning myocardial infarction but no advantage for cerebral vascular accidents. Besides, in both studies an additional risk of haemorrhagic cerebral vascular accident was described. Methodological reasons were the origin of these facts, but it resulted in a certain confusion as to the practical conduct to adopt. Ten years later it is much more clear after the publication of three supplementary trials. The benefits of aspirin in terms of prevention of myocardial infarction are certain and considerable, at the price of a haemorrhagic risk equally certain but moderate. On the other hand, questions remain concerning the preventive effect of aspirin on cerebral vascular accidents and also on the expected benefits in the female sex. In practice, the prescription of aspirin with the objective of primary prevention must take into account the absolute benefit which can be expected. This is a function of the individual absolute risk before treatment which therefore signifies an evaluation based on the risk factors. Only subjects exposed to a substantial risk before treatment are likely to benefit from aspirin. For the others, the risks linked with aspirin could counterbalance its preventive advantages.

Renin-angiotensin system in two genetically normotensive strains of Lyon rats.

Compared to the Lyon normotensive (LN) controls, adult Lyon hypertensive rats (LH) exhibit a renin-angiotensin system (RAS) dependent hypertension despite a low renin secretion. This discrepancy could be explained by the elevated slow pressor response to angiotensin II (AII) found in LH rats compared to LN controls. To evaluate more precisely the pathophysiological importance of this increased response, the present work aimed at determining whether the characteristics of the RAS were identical in LN and low blood pressure (LL) rats, the other normotensive control strain simultaneously selected with LH rats. Plasma and kidney renin and prorenin were measured in 11-week-old LN and LL rats. Aortic blood pressure (BP) was recorded at 15 weeks of age in freely moving rats of both strains either untreated or having received an angiotensin converting enzyme inhibitor, perindopril (3 mg/kg/day orally) since the age of 3 weeks. Acute dose-response curves were constructed for AII and norepinephrine (NE). The long-term pressor effects of AII (200 ng/kg/ min) and NE (1000 ng/kg/min) were measured after chronic infusions in perindopril-treated LN and LL rats. LN and LL rats exhibited similar mean BP level before (114 +/- 2 and 117 +/- 2 mm Hg, respectively) and after perindopril treatment (91 +/-3 and 93 +/- 1 mm Hg, respectively). Plasma and kidney renin and prorenin were decreased in LL rats. In acute conditions, LL rats exhibited an unspecific hypersensitivity to AII and NE. Chronically given AII exerted a greater pressor effect in LL than in LN rats after 4 weeks (113 +/- 3 v 97 +/- 5 mm Hg in LL and LN rats respectively, P < .05) and, even more, after 8 weeks of infusion (144 +/- 9 v 124 +/- 4 mm Hg in LL and LN rats respectively, P < .05). The NE was devoid of chronic pressor effects. In conclusion, 1) the increased slow pressor response to AII may not be a critical pathogenetic factor in the development of hypertension, as it also exists in normotensive LL rats; 2) LN and LL rats have the same normal BP despite marked differences in their RAS, thus suggesting that there could be several forms of normotension as known for hypertension; and 3) the simple comparison between one genetically hypertensive strain and one single normotensive control strain does not allow one to conclude that a phenotypic difference is of pathophysiological significance.

Difference between office and ambulatory blood pressure or real white coat effect: does it matter in terms of prognosis?

OBJECTIVE: The blood pressure (BP) response to the doctor's visit, generally referred as the white coat (WC) response, is usually estimated by the difference between office BP (OBP) and ambulatory BP (ABP). The purpose of this study was to determine the validity of this estimation. To that end, we compared the real WC effect and the estimated WC effect (OBP-ABP) in terms of magnitude and consequences on target organs. DESIGN: The study comprised 88 patients referred for hypertension. The real WC effect was measured using a Finapres device and expressed as the maximal WC effect (Max WC) or the average WC effect (Aver WC). For the estimation of target organ damages, the whole hypertensive group was separated into two groups according to the medians of the Aver WC, the Max WC, and the estimated WC effects, successively. Left ventricular mass index, E to A mitral wave ratio and pulse wave velocity were compared between groups as were serum creatinine, cholesterol and glucose levels. RESULTS: The estimated WC effect proved to be a bad index of the real response to the doctor's visit as assessed by their difference of magnitude between the two (20 +/- 17, 12 +/- 12 and 30 +/- 14 mmHg as estimated WC, Aver WC and Max WC effects, respectively), their loose correlations (r=0.31, P=0.004 between estimated WC and Aver WC effects; r=0.27, P=0.01 between estimated WC and Max WC effects), and finally by the fact that they were in agreement in less than two-thirds of the patients for the categorization of the WC response. Concerning target organ damages, no difference in terms of cardiac mass, diastolic function, arterial distensibility, renal function and cardiovascular risk profile could be discerned between the groups with a high and a low WC effect, either real or estimated, when age and ABP were taken into account. CONCLUSION: The present work supports the view that the true WC effect and its estimation are not equivalent. However, the way in which the WC response is defined does not alter its effect on target organs or cardiovascular risk profile.

[Hypertension. New French recommendations]. / Hypertension artérielle. Les nouvelles recommandations françaises.

The field of hypertensive medicine is constantly and rapidly changing, especially with regards to treatment. In view of its high incidence and its complications, it is a major public health concern. This explains the periodic publication of national or international recommendations with the object of informing practitioners of the latest publications in a form applicable to clinical medicine. In France, the "Agence Nationale d'Accréditation et d'Evaluation en Santé" (ANAES) has recently published its recommendations for the management of hypertension. The dominant issues are the recognition of validated electronic sphygmomanometers for measuring the blood pressure in the out-patient setting, the evaluation of individual cardiovascular risk for treatment choice, the value of non-pharmacological interventions, the tailoring of antihypertensive treatment and the abandon of the concept of equal benefit of comparable blood pressure lowering irrespective of the molecule used.