Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation

It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open‐label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24‐hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day‐by‐day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N‐terminal pro‐brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk‐lowering effect against AF recurrence in paroxysmal AF hypertensive patients.     

Effects of Exercise Therapy Alone and in Combination with a Calcium Channel Blocker or an Angiotensin Receptor Blocker in Hypertensive Patients

We compared the effects of exercise alone and in combination with a calcium channel blocker (amlodipine) or an angiotensin receptor blocker (valsartan) in hypertensive patients. Our results indicated that exercise therapy exerted similar effects on systolic blood pressure whether administered alone or in combination with amlodipine or valsartan; however, diastolic blood pressure decreased significantly when exercise therapy was combined with amlodipine. However, when combined with valsartan, exercise therapy additionally improved the lipid profile of hypertensive patients. Thus, this study enabled the identification of the drugs suitable for combination with exercise therapy in the treatment of hypertensive patients.     

Age‐ and Sex‐Related Differences in Efficacy With an Angiotensin II Receptor Blocker and a Calcium Channel Blocker in Asian Hypertensive Patients

Overseas guidelines to manage hypertension recommend selecting different drugs depending on age, but no studies have investigated the relationship between drug selection and age‐ and sex‐related differences, although such information may help to reduce the risk of cardiovascular mortality. The Azilsartan Circadian and Sleep Pressure––the First Study (ACS1) trial was a multicentered, randomized, open‐label, two‐parallel group study comparing the effects of an angiotensin II receptor blocker (azilsartan) and a calcium channel blocker (amlodipine). The present study is a post hoc analysis of ACS1 to investigate age‐ and sex‐related differences in the antihypertensive effects between azilsartan and amlodipine. Azilsartan significantly reduced diastolic blood pressure in male patients younger than 60 years compared with amlodipine, but amlodipine significantly reduced systolic blood pressure in female patients 60 years and older compared with azilsartan. A randomized controlled trial to evaluate cardiovascular outcomes will demonstrate whether a diastolic blood pressure–lowering effect with azilsartan is significantly effective in male patients younger than 60 years.     

血管紧张素转换酶抑制剂联合钙离子通道阻滞剂在高血压治疗中的应用进展

高血压是一种临床常见的心血管综合征,由于其发病机制复杂,单药治疗血压控制达标率低,而联合治疗通过干预多种升压机制,不仅使血压控制达标率明显增高,而且具有良好的靶器官保护作用。研究表明在众多联合治疗方案中血管紧张素转换酶抑制剂联合钙离子通道阻滞剂可能是最优化的一种,现将对此进行综述。     

血管紧张素 II 受体阻滞剂治疗肥厚型心肌病的Meta 分析

目的 使用Meta分析的方法,评价血管紧张素Ⅱ受体拮抗剂（ARBs）类药物对肥厚型心肌病（HCM）的疗效。方法 检索Web of Science, PubMed, EMBASE,Cochrane Central Register of Controlled Trials,中国知网（CNKI）,中国生物医学文献光盘数据库（CBMdisk）的文献。纳入与安慰剂或常规治疗相比较的临床随机对照试验,分析ARB类药物治疗HCM的效果。结果 包括228例患者的6个随机对照试验纳入Meta分析,研究显示ARB类药物对于左室射血分数、二尖瓣舒张早期最大血流速度（E）与舒张晚期最大血流速度（A）及左室质量的影响未见统计学差异。结论 ARB类药物对于HCM患者的心脏功能可能没有影响。     

Three-Month Effects of Candesartan Cilexetil, an Angiotensin II Type 1 (AT1) Receptor Antagonist, on Left Ventricular Mass and Hemodynamics in Patients with Essential Hypertension

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2–8 mg/day orally for 8–12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 ± 17.2 mmHg (mean ± SD) to 150.2 ± 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 ± 6.5 mmHg to 87.8 ± 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 ± 31.3 g/m2 to 102.6 ± 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 ± 31.1 g/m2 to 115.8 ± 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 ± 636.3 dynes·s·cm–5 to 1540.4 ± 432.0 dynes·s·cm–5 (P = 0.0034) on MRI and from 1820.4 ± 318.8 dynes·s·cm–5 to 1659.0 ± 317.7 dynes·s·cm–5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2–8 mg/day orally for 8–12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.     

Role of Baroreceptor Resetting in the Tachycardia Observed During the Onset of One-Kidney,one Clip Hypertension

A previous study from our laboratory demonstrated the occurrence of transient tachycardia during the onset of one-kidney, one clip (1K1C) hypertension in conscious rats. In the present study, using electroneurographic recordings in anesthetized rats, we investigated the time course of baroreceptor resetting at the onset (3, 7, 14 and 21 days) of 1K-1C hypertension. No significant difference between the diastolic pressure and the systolic threshold pressure for baroreceptor activation was detected in normotensive control rats and hypertensive rats 3, 7, 14 and 21 days after clipping. These data indicate that the baroreceptors were completely reset to the hypertensive levels during the periods studied. The data also suggest that baroreceptor resetting may play a facilitating role in the onset of tachycardia and the development of 1K1C hypertension in the conscious animal model.     

Effects of a Calcium Channel Blocker,Nicardipine, on Pressure-Natriuresis in Dahl Salt-Sensitive Rats

The effects of a calcium channel blocker, nicardipine, on pressure-natriuresis responses were studied in Dahl salt sensitive (DS) and resistant (DR) rats. Differences in the neural and endocrine background were minimized by renal denervation and by holding plasma vasopressin, aldosterone, coricosterone, and norepinephrine levels constant by intravenous infusion. The renal plasma flow (RPF) and glomerular filtration rate (GFR) of DS rats were disautoregulated in the low renal perfusion pressure range, while those of DR rats were autoregulated. Administration of nicardipine (0.3 μ/kg/min) into the renal artery significantly increased RPF and GFR and abolished the autoregulation in both strains of rats. Nicardipine also sharpened the pressurenatriuresis responses in both strains without changes in fractional excretion of sodium. These findings suggest that nicardipine increased GFR and thereby improved the pressure-natriuresis responses of DS rats.     

Role of Angiotensin II in the Hypertension Induced by Renal Artery Stenosis

Identical degrees of renal artery stenosis were induced in 5 dogs on two separate occasions; once during continuous inhibition of angiotensin I converting enzyme with enalapril, and once with the dogs untreated. Arterial pressure rose about 25 mm Hg during 3 days of stenosis in untreated dogs, due to increased total peripheral resistance. When the dogs were treated with enalapril, blood pressure had risen 14.5 ± 3.4 mm Hg 24 hours after stenosis due to a 35% increase in cardiac output while total peripheral resistance fell by 16%. By the third day, blood pressure had returned to pre-stenosis levels, cardiac output was close to normal and total peripheral resistance had increased. The stenosis on the renal artery increased the resistance to blood flow of the kidneys in both untreated and enalapril treated dogs. This increase in kidney resistance in the untreated dogs accounted for about 30% of the change in total peripheral resistance. In the enalapril treated dogs, the increased kidney resistance helped offset the vasodilatation in the rest of the vasculature. These results suggest that angiotensin II mediated vasoconstriction of nonrenal vascular beds was responsible for about ? of the hypertension following renal artery stenosis, and the resistance of the stenosis responsible for about ?.     

Successful Radiofrequency Catheter Ablation of Sustained Ventricular Tachycardia Postmyocardial Infarction in Man Guided by a Multielectrode "Basket" Catheter

Multielectrode "Basket" Catheter. Currently, analysis of sustained ventricular tachycardia postmyocardial infarction in man is limited by the time required for single point activation mapping and the difficulty in obtaining information during hemodynamically unstable arrhythmias. To overcome these limitations, we developed a multielectrode "basket" catheter for endocardial recording and pacing. This report describes the first clinical use of such a catheter to guide successful radiofrequency ablation of incessant sustained ventricular tachycardia postmyocardial infarction. This system may significantly shorten the time required for VT analysis and improve the results of radiofrequency catheter ablation for VT postmyocardial infarction.     

Microwave Ablation of an Ischemic Sustained Ventricular Tachycardia During Aortocoronary Bypass,Mitral Valve and Tricuspid Valve Surgery Guided by a Three-Dimensional Nonfluoroscopic Mapping System (CARTO)

Postinfarct patients with malignant ventricular tachyarrhythmias (VTs) are prone to an increased risk for sudden cardiac death and implantation of an internal cardioverter-defibrillator (ICD) often is recommended. In cases where the VTs are incessant or refractory to medical treatment, disruption of the macro-reentry circuit, which represents the arrhythmogenic substrate for postinfarct VTs, is a major therapeutical goal for electrophysiologists. The precise identification of this underlying macro-reentrant circuit depends on conventional mapping techniques (i.e. diastolic potentials, entrainment) and more recently by a three-dimensional non-fluoroscopic electroanatomical mapping system (CARTO), which integrates anatomical and electrophysiological information to reconstruct a three-dimensional activation and propagation map of the relevant VT. This reports describes on a patient with recurrent, drug-refractory, hemodynamically stable monomorphic VTs on the basis of a 2-vessel coronary artery disease, reduced left ventricular ejection fraction, who was scheduled for coronary artery bypass graft operation combined with mitral valve replacement and reconstruction of the tricuspid valve. Preoperatively, the underlying mechanism of the VT was identified by CARTO mapping with a slow conduction zone and a wide exit site at the inferoapico-basal portion of the left ventricle. In close cooperation between the cardiologists and the surgeons the decision for a simultaneous ablation approach during the subsequent operation was made. Successful ablation of the VT using microwave energy was confirmed by non-inducibility of the VT in the perioperative electrophysiologic study. This case report highlightens the use of CARTO mapping to identify postinfarct VTs as well as the application of microwave energy as a useful tool to cure postinfarct ventricular arrhythmias. There is no conflict of interest or any financial support for the authors related to the present case report. Both authors contributed equally to the work.     

Successful Catheter Ablation and Documentation of the Activation and Propagation Pattern During a Left Atrial Focal Tachycardia in a Patient with Cor Triatriatum Sinister

Atrial Tachycardia in Cor Triatriatum. We report a case of an atrial tachycardia (AT) originating from the left atrium (LA) associated with cor triatriatum sinister. Electroanatomical mapping of the 2 subdivided chambers of the LA during the AT revealed a centrifugal activation pattern from the posterior wall of the accessory chamber near the left superior pulmonary vein. The propagation map on the CARTO system revealed that the AT wave front spread centrifugally over the “accessory chamber,” turned around the edge of the membrane subdividing the LA, and then spread over the “main chamber.” A single radiofrequency application successfully abolished the AT . (J Cardiovasc Electrophysiol, Vol. 21, pp. 1050‐1054, September 2010)     

Atrioventricular Node Reentrant Tachycardia in Patients With a Prolonged AH Interval During Sinus Rhythm: Clinical Features, Electrophysiologic Characteristics and Results of Radiofrequency Ablation

Among a consecutive series of 600 patients who underwent radiofrequency catheter ablation for AV node reentrant tachycardia, 14 patients (age 29-76 years) had a prolonged AH interval during sinus rhythm (172±18 ms, range 140 to 200). Seven of them had unsuccessful ablation during the previous ablation sessions. Eight patients with anterograde dual AV node pathway physiology received anterograde slow pathway ablation, and the other 6 patients without dual-pathway physiology received retrograde fast pathway ablation. All patients had successful elimination of AV nodal reentrant tachycardia after a mean of 4±4 radiofrequency applications, power level 36±6 watts and a pulse duration of 42±4 seconds. The postablation AH interval remained unchanged. During a follow-up period of 25±13 months, one patient who received slow pathway ablation developed 2:1 AV block with syncope. As compared with the other 586 patients without a prolonged AH interval, these 14 patients had significantly poorer anterograde AV nodal function and lower incidence of anterograde dual AV node physiology (P<0.01). We concluded that slow pathway ablation in patients with dual pathway physiology, and retrograde fast pathway ablation in patients without dual pathway physiology were effective and safe in patients with a prolonged AH interval. However, delayed onset of symptomatic AV block is possible and careful follow-up is necessary.     

Effects of an ACE Inhibitor and a Calcium Channel Blocker on Cardiovascular Autonomic Nervous System and Carotid Distensibility in Patients with Mild to Moderate Hypertension

We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 ± 1.9 → 5.6 ± 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 ± 0.8 → 2.5 ± 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.     

Beneficial Effects of L‐ and N‐type Calcium Channel Blocker on Glucose and Lipid Metabolism and Renal Function in Patients with Hypertension and Type II Diabetes Mellitus

It has been proved that cilnidipine has N‐type calcium channels inhibitory activity as well as L‐type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L‐type calcium channels) and cilnidipine (an inhibitor of both L‐type and N‐type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy‐seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA‐R) level in the non‐diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N‐type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function.     

Studies on The Role of Intracellular Sodium and Calcium in The Centrally Mediated Pressor Effects of CSF [Na+], Ouabain and Angiotensin II in Anesthetized Dogs

Cerebroventricular infusions of hyperosmotic Na⁺solutions, ouabain and/or Angiotensin-II produced significant increases in the arterial blood pressure in chloralose anesthetized, vagotomized dogs. A lower concentration of ouabain (10^?6M) which did not alter blood pressure, significantly potentiated the centrally mediated pressor effects of hyperosmotic Na⁺and angiotensin-II. Hence, the data suggested that the magnitude of the central pressor effects of Angiotensin-II or hyperosmotic Na⁺may depend upon net accumulation of sodium in the neuronal cells. Prior cerebroventricular infusions of felodipine, a “calcium antagonist,” significantly inhibited the pressor actions of higher concentrations of ouabain as well as that of hyperosomotic Na⁺- solutions, indicating that cellular calcium may be essential for triggering these central effects. These studies collectively indicate that disturbances in the Na⁺-transport in the neuronal cells may account for the involvement of the central nervous system in various types of hypertension.     

Effects of a Dual L/N-Type Calcium Channel Blocker Cilnidipine on Blood Pressure,Pulse Rate,and Autonomic Functions in Patients with Mild to Moderate Hypertension

The current study was conducted to examine the effects of cilnidipine, a dual L/N-type calcium channel blocker, on blood pressure, pulse rate, and autonomic functions in patients with mild-to-moderate hypertension. Sixteen patients with mild-to-moderate hypertension (8 males and 8 females; 44–72 years of age) were treated with cilnidipine (10 mg/day) for 3 months. Before and after the treatment, the following measurements were conducted; beat-to-beat blood pressure during late phase II and overshoot phase of the Valsalva maneuver, the Valsalva ratio, heart rate response to deep breathing, systolic and diastolic blood pressure, and pulse rate. The head-up tilt test was also performed before and after the treatment. Cilnidipine significantly decreased either the systolic or diastolic blood pressure from 151 ± 15 mmHg to 129 ± 14 mmHg or 84 ± 11 mmHg to 71 ± 9 mmHg, respectively. For pulse rate, there were no significant changes during therapy. Beat-to-beat blood pressure during late phase II and overshoot phase of the Valsalva maneuver indicated significant improvements in both figures. The heart rate response to deep breathing and the Valsalva ratio indicated no significant differences during therapy. Before and after the treatment, no orthostatic hypotension was observed during the head-up tilt test. The current study revealed that cilnidipine significantly decreases blood pressure with improving autonomic functions while having no adverse effects on heart rate response and pulse rate.