Michael Frank

Eligibility for renal denervation in patients with resistant hypertension: when enthusiasm meets reality in real-life patients.

To the Editor: Percutaneous renal sympathetic denervation (RDN) by radiofrequency ablation is a novel therapeutic intervention that has been shown to decrease blood pressure (BP) significantly ([1][1]) and persistently ([2][2]) in patients with resistant hypertension (RH). However, the evidence

Endothelium-derived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels

OBJECTIVES We sought to determine whether endothelium-derived relaxing factor (nitric oxide) exerts a tonic vasodilating effect on coronary collateral channels developed in response to myocardial ischemia. BACKGROUND Although the coronary collateral circulation is known to react to several vasoactive agents, the role of endogenously produced nitric oxide is unclear. METHODS Coronary collateral channels were induced in the left circumflex artery bed of 12 chronically instrumented dogs by either ameroid implantation or repeated occlusion of the left circumflex coronary artery. With the native circumflex artery occluded, aortic and circumflex pressures and microsphere flows were measured before and after systemic administration of NG-nitro-L-arginine methyl ester, an arginine analogue known to block the synthesis of nitric oxide. RESULTS NG-nitro-L-arginine methyl ester increased mean aortic pressure from a mean +/- SEM of 92 +/- 4 to 114 +/- 4 mm Hg, whereas pressure in the occluded circumflex artery decreased from 61 +/- 4 to 55 +/- 4 mm Hg. The increase in aortic-circumflex pressure gradient (from 31 +/- 4 to 59 +/- 5 mm Hg) was accompanied by a decrease in flow in the circumflex bed (from 1.31 to +/- 0.14 to 1.09 +/- 0.15 ml/min per g), resulting in an increase in coronary collateral resistance averaging 173 +/- 37% (from 26 +/- 4 to 64 +/- 9 mm Hg/ml per min per g, p < 0.01). The increase in collateral resistance could be partially reversed by administration of L-arginine. CONCLUSIONS We conclude that nitric oxide normally exerts a substantial tonic dilating effect in coronary collateral vessels. Disease-induced alterations in endothelial function may limit collateral perfusion importantly.

Lymphoepithelioma-like carcinoma of the lung

Primary lymphoepithelioma-like carcinoma of the lung is rare; only 26 case reports have been identified in the literature. The present report presents a case of a 67-year-old white man with a T1 N1 M0 lymphoepithelioma-like carcinoma of the lung. He presented with severe arthritic complaints that resolved after resection of the tumor. The majority of these tumors have occurred in Asian patients who have shown evidence of previous exposure to the Epstein-Barr virus.

Repair of Mitral Valve and Subaortic Mycotic Aneurysm in a Child With Endocarditis

Endocarditis requiring surgical intervention in children is uncommon. Individualized operative therapy must be fashioned to the particular pathology of each case. In this case we describe mitral anterior leaflet homograft patch augmentation valvuloplasty, subaortic homograft patch closure of a large mycotic aneurysm, and homograft aortic root replacement in a 3-year-old patient with endocarditis after remote repair of complete atrioventricular canal.

True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence.

Objectives: We assessed the influence of medication adherence on blood pressure (BP) control and target organ damage in a pre-specified analysis of a published trial comparing sequential nephron blockade (SNB) or sequential renin–angiotensin system blockade (SRASB) in patients with resistant hypertension. Methods: Patients were randomized to SNB (n = 82) or SRASB (n = 82) and studied at baseline and after 12 weeks. BP was measured by ambulatory blood pressure monitoring. Carotid–femoral pulse wave velocity (PWV) was measured by applanation tonometry and left ventricular mass (LVM) by echocardiography. Low medication adherence was assessed through plasma irbesartan concentration below 20 ng/ml; urinary N-acetyl-seryl-aspartyl-lysyl-proline/creatinine ratio below 4 nmol/mmol; last medication intake before visit greater than 24 h and pill counting below 80% of theoretical intake. Medication adherence score (sum of items, max = 4) is defined as low (medication adherence score <2) or acceptable (medication adherence score ≥2). Results: Among 164 patients, 134 (81.7%) had acceptable medication adherence and 30 (18.3%) low medication adherence, with similar proportions in the SNB and SRASB arms. After 12 weeks, in patients with acceptable medication adherence, BP was more frequently controlled in those treated with SNB (64%), than SRASB (18%; P < 0.001). The difference in daytime SBP was −11.5 mmHg [95% confidence interval (CI) −15.4 to −7.5, P < 0.0001] in patients with acceptable medication adherence. In contrast, in patients with low medication adherence, the difference between groups was smaller and not significant (−9.4 mmHg, 95% CI −20.4 to 1.7, P = 0.09). Independently of BP changes, PWV and LVM decreased more in the SNB than in the SRASB arm when medication adherence was acceptable (−0.52 m/s, 95% CI −1.3 to −0.007, P = 0.047; and −24 g/m2, 95% CI −36 to −12, P = 0.0003), whereas no significant changes were observed in low medication adherence patients. Conclusion: Medication adherence contributes to BP-lowering and regression of target organ damage. The differential effects of SNB and SRASB is observed in patients with acceptable medication adherence, and not in patients with low medication adherence.

Greater efficacy of aldosterone blockade and diuretic reinforcement vs. dual renin-angiotensin blockade for left ventricular mass regression in patients with resistant hypertension.

Objectives: We report the results of an echocardiographic substudy carried out in a trial comparing the effects of two different treatment strategies – mineralocorticoid receptor blockade (MRB) and dual renin–angiotensin system blockade (RASB) – in patients with resistant hypertension. Both strategies reduce left ventricular mass index (LVMI), but they have not been compared in patients with resistant hypertension. Methods: After 4-week treatment with 300 mg irbesartan + 12.5 mg hydrochorothiazide + 5 mg amlodipine, 86 patients with resistant hypertension were randomized to the add-on 25 mg spironolactone (MRB group, n = 46) or 5 mg ramipril (RASB group, n = 40) groups for 12 weeks. Treatment intensity was increased at week 4, 8 or 10 if home blood pressure (BP) was equal to or above 135/85 mmHg, by sequentially adding 20–40 mg furosemide and 5 mg amiloride (MRB group), or 10 mg ramipril and 5–10 mg bisoprolol (RASB group). Transthoracic echography was performed at baseline and week 12. Results: Daytime ambulatory BP decreased by 19 ± 12/11 ± 8 mmHg in the MRB group and by 8 ± 13/7 ± 7 mmHg in the RASB group (P = 0.0003/0.03). LVMI decreased by 8.2 ± 18.9 g/m2 in the MRB group, whereas it increased by 1.8 ± 19.1 g/m2 in the RASB group (P = 0.03). The decreases in posterior wall thickness, left ventricular (LV) end-systolic diameter, E/e′ ratio and left atrial area were significantly greater with MRB than with RASB. The difference between groups remained significant after adjustment for the decrease in ambulatory BP. Conclusion: In patients with resistant hypertension, MRB-based treatment decreased both BP and LVMI more efficiently than a strategy based on dual RASB.