[Chronic pheochromocytoma-induced myocardial injuries: What should we expect from modern and classical echocardiographic tools?] / Apport du 2D strain et des outils échocardiographiques classiques pour la recherche d'anomalies myocardiques induites par l'exposition chronique à un phéochromocytome.

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.

[Alteration of left ventricular longitudinal systolic function in 2D-strain in primary aldosteronism: A new target organ damage marker]. / Altération de la fonction systolique longitudinale du ventricule gauche en strain bidimensionnel dans l'hyperaldostéronisme primaire : un nouveau marqueur d'atteinte d'organe cible.

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/m2 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.

From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency.

The prevalence of malignant hypertension has clearly fallen with the advent of anti-hypertensive medication but has remained stable over the past 30-40 years in spite of progress in diagnosis and management of hypertension. A diagnosis of malignant hypertension is usually based on the association of severely elevated blood pressure with a Keith and Wagener stage III or IV retinopathy. We believe that this definition can be reconsidered for several reasons. Although simple and pragmatic, this definition corresponds to a time when there were few techniques for assessment of hypertensive target organ involvement, and does not take into account involvement of kidney, brain and heart; whereas the overall prognosis largely depends on how much they are affected. On the contrary, the acute blood pressure level and especially diastolic should not be a hard diagnostic criterion as it does not itself constitute the prognosis of the condition. We propose to consider that malignant hypertension with retinopathy is only one of a number of possible presentation(s) of acute hypertension with multi organ damage (hypertension multi organ damage (MOD)) and that the recognition of these hypertensive emergencies, when retinopathy is lacking, be based on acute elevation of BP associated with impairment of at least three different target organs. The objective of a new and expanded definition is to facilitate recognition of these true emergencies. The condition is more common than usually perceived and would have a much worse prognosis than the usual forms of hypertension. Early recognition and management of hypertension-MOD are fundamental to any improvement in prognosis.

Impairment of skin blood flow during post-occlusive reactive hyperhemy assessed by laser Doppler flowmetry correlates with renal resistive index.

We lack non-invasive tools for evaluating the coronary and renal microcirculations. Since cutaneous Doppler laser exploration has evidenced impaired cutaneous microvascular responses in coronary artery disease and in impaired renal function, we wanted to find out if there was a link between the impairments in the cutaneous and renal microcirculations. To specify the significance of the rise in the renal resistive index (RI), which is still unclear, we also sought relations between RI and arterial stiffness. We conducted a cross-sectional controlled study in a heterogeneous population including hypertensive patients of various ages with or without a history of cardiovascular disease along with a healthy control group. The cutaneous microcirculation was evaluated by laser Doppler flowmetry of the post-occlusive reactive hyperhemy (PORH) and of the hyperhemy to heat. The renal microcirculation was evaluated by measurement of the RI. Arterial stiffness was evaluated from an ambulatory measurement of the corrected QKD(100-60) interval. We included 22 hypertensives and 11 controls of mean age 60.6 vs 40.8 years. In this population, there was a correlation between RI and basal zero to peak flow variation (BZ-PF) (r=-0.42; P=0.02) and a correlation between RI and rest flow to peak flow variation (RF-PF) (r=-0.44; P=0.01). There was also a significant correlation between RI and the corrected QKD(100-60) (r=-0.47; P=0.01). The significant correlation between PORH parameters and RI indicates that the functional modifications of the renal and cutaneous microcirculations tend to evolve in parallel during ageing or hypertension. The relation between RI and arterial stiffness shows that RI is a compound index of both renal microvascular impairment and the deterioration of macrovascular mechanics.

Domestic activities after myocardial infarction. Their impact is underestimated.

BACKGROUND: Although aptitude for resumption of work is usually evaluated after myocardial infarction, the return home often entails significant daily obligations whose cardiovascular implications are poorly described and may well be underestimated. AIM: The aim of this study was to evaluate the consequences of domestic activities on blood pressure and heart rate in patients with recent myocardial infarction DESIGN: This was an observational study. SETTING: Inpatients, at the end of a three week period of cardiovascular rehabilitation. POPULATION: Patients with recent myocardial infarction. METHODS: We studied patients who had benefited from a three-week period of cardiovascular rehabilitation after a myocardial infarction, all treated with beta-blockers. At the end of the rehabilitation period, patients were submitted to a standardized exercise test with measurement of V.O2. They also carried out, on a separate day, four standardized domestic tasks in a random order along with an automated measurement of blood pressure and heart rate. RESULTS: We included 16 men and 11 women, aged 35 to 74 years. Vacuum cleaning led to a much greater increase in the product of heart rate and systolic blood pressure (DP) than did window cleaning, bathroom cleaning or ironing. It also led to an increase in heart rate to 70-90% of maximum heart rate during the exercise test and 47-65% of the maximal DP on the exercise test. Although the women were more accustomed to these tasks than the men, they did not appear to benefit from any training effect. The average level of DP observed in some patients during domestic tasks was comparable to that of a maximum exercise test indicating that they were not adequately prepared for a return to household activities. CONCLUSION: Domestic tasks should not be underestimated as they can lead to a significant increase in DP. They tend not to be taken into account in the rehabilitation of patients after a myocardial infarction. CLINICAL REHABILITATION IMPACT: The traditional methods of rehabilitation are not well adapted for resumption of domestic life, especially for women who are most involved in these activities. We recommend an individual approach involving performance of real life tasks taking account of the personality of the patients, their lifestyle and home environment.

Metabolic syndrome and short-term and long-term heart rate variability in elderly free of clinical cardiovascular disease: the PROOF study.

OBJECTIVE: Autonomic nervous system (ANS) activity decrease has been associated with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we explored the relationship between ANS control of the cardiovascular system and metabolic syndrome. METHODS: We analyzed the relationship with both short-term and long-term heart rate variability (HRV) and metabolic syndrome in the cross-sectional PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants of the city of Saint Etienne, France, aged 65.6 ± 0.8 years at the inclusion date. Physical examination included measurements of height, weight, systolic and diastolic blood pressure, waist circumference, and biological parameters. HRV variables were measured over 5-min, nighttime, and 24-h periods using Holter monitoring. RESULTS: After adjustment for current type 2 diabetes, depression, and smoking, we found that metabolic syndrome status, high-density lipoprotein cholesterol (HDL-C), and waist circumference were significantly (p < 0.05) associated with total power, very-low frequency, low-frequency/high-frequency (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were significantly associated with decreased long-term HRV variables. Both nighttime and 24-h HRV showed closer associations with metabolic syndrome than did short-term HRV (5-min). Metabolic syndrome severity was associated with a decrease in both the long-term and short-term HRV variables. CONCLUSIONS: ANS control alteration of the cardiovascular system was more pronounced when evaluated by long-term than short-term HRV recordings, particularly in women.

[Surgical excision of subclinical cortisol secreting incidentalomas: Impact on blood pressure, BMI and glucose metabolism]. / Bénéfices tensionnels, anthropométriques et métaboliques de l'exérèse chirurgicale des adénomes cortisoliques infracliniques.

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.

Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials.

Cardiovascular risk is subject to circadian variation, with peak morning incidence of myocardial infarction and stroke correlating with the early morning blood pressure (BP) surge (EMBPS). Ideally, antihypertensive therapy should maintain control of BP throughout the 24-h dosing cycle. In two sister studies, Prospective, Randomized Investigation of the Safety and efficacy of Micardis vs Ramipril Using ABPM (ambulatory BP monitoring) (PRISMA) I and II, BP control was compared in patients with essential hypertension (24-h mean baseline ambulatory BP approximately 148/93 mm Hg) randomized to the angiotensin receptor blocker, telmisartan (80 mg; n=802), or the angiotensin-converting enzyme inhibitor, ramipril (5 or 10 mg; n=811), both dosed in the morning. The primary end point was the change from baseline in mean ambulatory systolic BP (SBP) and diastolic BP (DBP) during the final 6 h of the 24-h dosing cycle. The adjusted mean treatment differences in the last 6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons). Secondary end point results, including the mean 24-h ambulatory BP monitoring, day- and night-time BP and 24-h BP load, also significantly favoured telmisartan (P<0.0001). Both treatments were well tolerated; adverse events, including cough, were less common with telmisartan. These findings suggest that telmisartan is more effective than ramipril throughout the 24-h period and during the EMBPS; this may be attributable to telmisartan's long duration of effect, which is sustained throughout the 24-h dosing period.

Preparation for surgery of phaeochromocytoma by blockade of alpha-adrenergic receptors with urapidil: what dose?

The preparation for phaeochromocytoma surgery is a matter of debate. Pre-operative blockade of alpha-1 receptors is increasingly employed in an attempt to reduce the risk of hypertensive episodes, especially during manipulation of the tumour. In this study, we compared the interest of an almost complete blockade of these receptors by high doses of urapidil in comparison with that of moderate doses of this drug. The study was conducted in two consecutive series of 18 patients, the first treated by a moderate dose, and the second by the highest dose tolerated by the patient. The two groups were comparable in other respects. All patients were operated under laparoscopy by the same surgeon and managed by the same anaesthetist using the same protocol. The number of hypertensive peaks was significantly reduced using the high dose of urapidil, with no more hypotensive episodes after tumour removal in this group. The area under the curve of norepinephrine levels as a function of time was significantly larger with the high doses of urapidil, arguing in favour of a more complete blockade of alpha-1 receptors. Our findings indicate the value of aggressive blockade of alpha-1 receptors in preparation for surgery of phaeochromocytoma.

Magnitude of the early morning blood pressure surge in untreated hypertensive patients: a pooled analysis.

OBJECTIVES: A post hoc analysis was performed to assess the magnitude of the early morning blood pressure surge (EMBPS), which is associated with peak cardiovascular risk, in untreated hypertensive patients enrolled in two sister studies (Prospective, Randomised Investigation of the Safety and efficacy of MICARDIS vs. ramipril using ambulatory blood pressure monitoring I and II) with identical design. METHODS: In adults with a mild-to-moderate primary hypertension and no significant comorbidities, 24-h ambulatory blood pressure monitoring was conducted after a 2- to 4-week placebo run-in period and before treatment initiation. Individual blood pressure measurements at 20-min intervals were analysed. RESULTS: In 1419 hypertensive patients with normal sleeping times, blood pressure displayed a typical circadian rhythm, with a mean EMBPS of 29/24 mmHg. An EMBPS of >or= 25 mmHg was observed in around 60% of patients. The surge was significantly increased with smoking, alcohol consumption, longer sleep, later waking times, and increased blood pressure variability during waking and sleeping. The magnitude of the EMBPS was significantly reduced in Black vs. White patients. The surge was not affected by gender, body mass index or duration of hypertension. Further analysis showed that ethnicity, alcohol consumption and smoking were all found to have a significant impact on surge around waking and age, sleep duration and sleep blood pressure variability were all found to have an effect on the prewake surge. CONCLUSIONS: In untreated hypertensive patients, the magnitude of the EMBPS is significant when compared with the 24-h mean and is affected by individual patient characteristics. In light of these findings, physicians should understand the importance of 24-h blood pressure control and the modification of certain lifestyle factors as ways of reducing the EMBPS.

[Prognostic value of QKD interval corrected by QRS duration in hypertensive patients]. / Valeur pronosfique de l'intervalle QKD: intérêt d'une correction par la largeur du QRS.

OBJECTIVES: The QKD interval is measured between the onset of QRS on the ECG and detection of last Korotkoff sound by a microphone placed on the brachial artery while measuring BP. It is the sum of preejection time and pulse transmission time and thus is correlated to pulse wave velocity (PWV). This interval is automatically monitored with BP and HR every 15 minutes during 24 h with an ambulatory blood pressure monitoring device (Diasys integra, Novacor, France). The 96 measurements obtained allow to automatically calculate the QKD(100-60), QKD value for 100 mmHg SBP and 60 bpm HR. This indice of arterial stiffness has been shown to be linked to future cardiovascular (CV) events, independently of 24 h BP. However this interval may be abnormally prolonged in case of left bundle branch blocks (LBBB). METHODS: We tested the effects of simply removing QRS duration from QKD(100-60) value on the prediction of CV events in a population of 412 hypertensives (247 males: age = 53 +/- 14 years; office BP = 158 +/- 19/97 +/- 11 mmHg; 24 h BP = 133 +/- 17/86 +/- 11 mmHg) followed prospectively. RESULTS: Mean follow up was 65 months, 32 pts were lost, 49 CV events occurred including 11 deaths. Cox model showed that baseline QKD(100-60) (m = 202 +/- 19; 142-254 ms) was significantly (p < 0.05) associated to events independently of age, 24h SBP and other traditional risk factors. Removing QRS duration (m = 85 +/- 10: 61-158 ms) improves the relation to events (monovariate khi2 = 38 vs 30). CONCLUSION: Removing QRS duration from QKD(100-60) improves its predictive value of future CV events and allows using this method in patients with LBBB.

Left ventricular hypertrophy--the problem and possible solutions.

Left ventricular hypertrophy (LVH), which describes pathological changes in cardiac structure, is a powerful and reversible predictor of cardiovascular risk. There is a continuous relationship between left ventricular mass (LVM) and the likelihood of cardiovascular events, with no cut-off between the absence of such events and heightened risk. A correlation between LVH and blood pressure is well established. There is a paradox, however, that the structural changes to the heart as a result of increased workload due to high blood pressure appear to promote cardiovascular disease. This may be partially explained by the fact that ambulatory blood pressure measurements correlate more closely with LVH than resting blood pressure. Blood pressure variation throughout the day is also emerging as an important correlate of LVH, and a strong association has been identified between an early morning rise in blood pressure and increased LVM. Use of anti-hypertensive agents not only lowers blood pressure, but can also bring about LVH regression. The pathological role of angiotensin II in LVH and target-organ damage within the cardiovascular continuum suggest that agents targeting the renin angiotensin-aldosterone system (RAAS), such as the angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, may prove particularly effective and may confer beneficial effects in addition to the lowering of blood pressure. The angiotensin II receptor blockers may be very appropriate treatment options because of their placebo-like tolerability and the possibility of more complete blockade of the RAAS. Within this class of anti-hypertensive agents, pharmacological differences may mean that some agents afford greater cardioprotection than others.

[Arterial rigidity of patients operated successfully for coarctation of the aorta without residual hypertension]. / Etude de la rigidité artérielle des patients opérés avec succès d'une coarctation de l'aorte sans hypertension résiduelle.

In patients successfully operated for coarctation of the aorta, the prevalence of hypertension is higher than that observed in the general population although the exact mechanism is not known. The hypothesis of increased arterial rigidity despite satisfactory correction of the coarctation has been proposed. The authors undertook 24 hour ambulatory blood pressure monitoring coupled with measurement of the QKD interval (pulse wave velocity) in order to evaluate the rigidity of the large arteries. These results were compared with those obtained in control patients paired with respect to gender, age, height and weight. Twenty-six patients with an average age of 14.5 +/- 2.9 years were included (age at time of surgery 6.3 +/- 3.7 years). The statistical data confirmed a higher systolic blood pressure (p<0.05) in the operated patients compared with controls. The results confirm the hypothesis of increased residual arterial rigidity in children operated for coarctation of the aorta which could predispose to secondary hypertension, especially on effort. In the long term, this could be an unquestionable cardiovascular risk factor explaining the increased cardiovascular morbid-mortality compared with the general population.

[Biochemical detection of Conn's adenoma: definition of criteria and reference values]. / Dépistage biologique des adénomes de Conn: definition des critères et des seuils.

Primary hyperaldosteronism is a diagnosis which should be considered in refractory hypertension even in the absence of any hypokalaemia. Its detection relies above all on the levels of renin and aldosterone. The aldosterone/renin ratio has been proposed as the most sensitive criterium. The reference values used for the diagnosis of primary hyperaldosteronism are very variable in the literature, depending not only on the method used but also on the criteria used for their determination. In this study we evaluated the defined reference values prospectively by studying a population of patients with a Conn's adenoma treated surgically. The study included an initial retrospective period which allowed identification of 29 cases of Conn's adenoma treated surgically, and a 9 month prospective period during which 212 reports were collected. During this prospective period a further 9 cases of Conn's adenoma were detected, which were successfully treated with surgery. Analysis to discriminate the 38 Conn's adenomata from the rest showed that 3 parameters contributed significantly and independently to the diagnosis: supine plasma renin activity (ARPc), supine aldosteronaemia and the erect aldosterone/renin ratio, allowing correct classification in 88% of the cases. The reference ranges of these 3 parameters were calculated in order to give a sensitivity of 100% and the best possible specificity, therefore allowing a combined criterium involving all 3 parameters to be defined: ARPc < 0.45 ng/ml/h, supine aldosteronaemia >417 pmol/l, and erect aldosterone/renin >1180.

[Malignant hypertension. Case series of 42 patients]. / Hypertension artérielle maligne.

One could expect that malignant hypertension would belong to the history. Unfortunately, this complication has not been eradicated even though many physicians have already forgot it. The hypertension care units are still confronted to it, and even the arrival of the renin-angiotensin system blockers have changed the prognosis of those patients, an adequate management on emergency remains mandatory in order to avoid in particular the evolution to renal failure. By reporting a series of 42 patients included in a period of 7 years, we aimed to remind the presentation of this severe pattern of hypertension and the basics of its management.

Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma.

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.