Prognostic Evaluation of QT-Dispersion in Elderly Hypertensive and Normotensive Patients

Background: QT‐corrected interval dispersion (QTcD) is an indirect index of increased heterogeneity of ventricular repolarization. However, the prognostic value of (QTcD) in elderly hypertensive and normotensive patients has not been thoroughly investigated yet. Methods: The study population consisted of 60 consecutive patients (34 males/26 females; mean age: 63±11 years) with mild to moderate essential arterial hypertension and 48 consecutive age‐matched healthy subjects (24 males/24 females; 65±16 years). QTcD was measured by a 12‐lead electrocardiogram (ECG) as the difference between maximum and minimum QT‐interval, corrected for heart rate. Ventricular arrhythmias were recorded by a 24‐hour Holter ECG and classified by a modified Lown's score (range: 0–6). Left ventricular mass was measured echocardiographically and indexed by body surface area [left ventricular mass index (LVMI)]. Nine patients were lost during the follow‐up period. Patients were followed up for 54±9 months, and the primary end‐point was the major cardiovascular events (including cardiac mortality). Results: Major cardiovascular events occurred in 22 patients (22%). Patients with QTcD ≥45 ms (n = 35) had a higher rate of major cardiovascular events (43% vs 11%; log rank: 14.8; P < 0.001), a higher LVMI (146±29 vs 104±21 g/m²; P < 0.001), greater values of systolic and diastolic blood pressure (154±16 vs 144±18 mmHg; P < 0.01 and 92±10 vs 88±8 mmHg; P < 0.05, respectively), a higher number of premature ventricular beats (354±870 vs 113±301; P < 0.05), and a greater Lown's score (3.7±1.9 vs 1.4±1.8; P < 0.05) than patients with QTcD <45 ms. QTcD (≥ or < 45 ms) was an independent predictor of major cardiovascular events (odds ratio: 4.9; 95% confidence interval: 2.0–12.1; P = 0.001) after adjustment for LVMI, Lown's score (≥ or <3), age (≥ or <65 years), and QTc max (≥ or <437 ms). Conclusions: QTcD is an independent predictor of major cardiovascular events in elderly hypertensive and normotensive patients and might be used in their risk stratification.     

Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide

The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH₂, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu¹⁵)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloro-methane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide.     

Long–Term Effect of VVI Pacing on Atrial and Ventricular Function in Patients with Sick Sinus Syndrome

We conducted a prospective, 6–month echocardiographic study on the effect of WI pacing on left atrial and ventricular function and dimensions in patients with sick sinus syndrome. Thirty nine patients (23 women and 16 men, aged 71.7 ± 9.2 years; 30 in sinus rhythm and 9 in atrial fibrillation) who had a WI pacemaker implanted because of sick sinus syndrome were recruited in the study. In 26 patients who presented with and remained in sinus rhythm, paced left ventricular ejection fraction and stroke volume were significantly decreased (71.4%± 11.8% to 67.0%± 13.6%, and 73.9 ± 29.0 cm³ to 66.3 ±21.1 cm³, respectively, P < 0.001 for both), whereas the paced diastolic dimension of the left atrium was significantly increased (3.2 ± 0.7 cm to 3.7 ± 0.9 cm, P < 0.001) at 6 months as compared with preimplantation. In nine patients with atrial fibrillation at implantation, paced left ventricular ejection fraction at follow–up was significantly decreased (67.7%±10.1% to 64.2%± 10.6%, P = 0.003), but paced stroke volume and left atrial diastolic dimension were not significantly changed (75.1 ± 25.6 cm³ to 79.0 ± 22.7 cm³, and 4.3 ±1.2 cm to 4.6 ±1.5 cm, P = NS for both) at follow–up. Cessation of pacing and restoration of sinus rhythm in 21 patients at follow–up did not result in any significant change of ejection fraction (67.5%± 10.2% to 67.6%± 9.7%, P = NS) whereas stroke volume was increased (59.1 ± 19.6 cm³ to 69.1 ± 22.3 cm³, P < 0.0001) in comparison with paced values. However, compared with preimplantation values, ejection fraction was significantly decreased (70.4%± 10.0% to 67.6%± 9.7%, P = 0.001), whereas stroke volume was not significantly changed (68.4 ± 22.3 cm³ to 69.1 ± 22.3 cm³, P = NS) during sinus rhythm at follow–up. In 14 of those patients, discontinuation of pacing resulted in a significant increase of left atrial fractional shortening (8.1 %± 1.7% to 20.1 %± 4.3%, P < 0.001) and significant increase of left atrial diastolic dimension compared with paced and preimplantation levels (3.8 ± 0.7 cm vs 3.6 ± 0.7 cm and 3.0 ± 0.5 cm, respectively, P < 0.001). Long–term WI pacing in patients with sick sinus syndrome results in increase of the left ventricular end–systolic dimension and permanent reduction of the left ventricular ejection fraction. In the left atrium, WI pacing causes an immediate reduction of the fractional shortening as well as long–term increase of the diastolic dimension.     

Intervention in Hypertrophic Obstructive Cardiomyopathy

This article reviews the present status of intervention in hypertrophic obstructive cardiomyopathy. Interventions include pacing, which is best administered by VDD mode with sufficiently short atrioventricular delay as to assure ventricular capture. Occasionally, this may require the addition of atrioiventricular (AV) junctional ablation in order to achieve 100% ventricular capture. This approach alters the left ventricular (LV) contraction sequence, thereby reducing the left ventricular outflow obstruction. VVI pacing is inadequate because of the necessity for atrial contribution to the hypertrophied ventricle. This contribution may he ineffective even with VDD pacing, without the benefit of AV junctional ablation, because of late activation of the left atrium. Ablation of the left bundle branch may also achieve altered contraction sequence of the LV, but experience with this technique is very limited. Two different methods of reduction of the interventricular septum have been proposed. The first is transaortic laser, which has not gained wide acceptance, and the second is a new and promising method that appears to be less traumatic. This is alcohol delivery to the first septal branch of the left anterior descending coronary artery by an angioplasty technique. Surgical approaches include septal myomectomy directly to reduce the obstruction and mitral valve replacement to eliminate the part played in the obstruction by the anterior cusp of the valve. In conclusion, younger patients, even those who are asymptomatic, should be considered for surgical myomectomy, there being little place now for mitral valve replacement. In older patients, pacing and septal chemoablation offer the greatest promise, but their places are not yet fully established . (J Interven Cardiol 1996; 9:399–403)