Selective Imidazoline Receptor Agonists: redefining the role of centrally acting agents in management of hypertension

Hypertension, often referred to as ‘The silent killer’, is christened so, as it is seldom preceded by any warning signs or symptoms. With the new ACC/AHA guidelines lowering the Blood Pressure (BP) threshold values, it has resulted in a 140% relative increase in the hypertension prevalence in India, which is 3 times higher than that of in United States. Imidazoline receptor agonists control BP effectively with minimal adverse effects of sedation and mental depression that are usually associated with centrally acting antihypertensives. While having a low affinity to the α2-adrenergic receptors, these new generation centrally acting antihypertensive agents are highly selective for imidazoline receptor. Moxonidine, a second-generation centrally acting antihypertensive drug having selective agonist activity on imidazoline I1 receptors and minor activity on imidazoline α2 adrenoceptors, reduces the activity of Sympathetic Nervous System (SNS) by activating I1 imidazoline receptors in Rostral Ventrolateral Medulla (RVLM). Studies of moxonidine have shown equal effectiveness in lowering BP like other well-established antihypertensive drugs such as nifedipine, atenolol or angiotensin-converting enzyme inhibitors, with minimal adverse events. At doses of 0.2-0.6 mg, moxonidine induces satisfactory BP reduction in patients with mild-to-moderate essential hypertension. In patients with mild-to-moderate hypertension, moxonidine (0.2-0.4 mg o.d.) significantly decreased Systolic Blood Pressure/Diastolic Blood Pressure (SBP/DBP), respectively, by 19.5/11.6 mmHg. In obese, non-controlled hypertensive patients, there is a 14% and 13.5% reduction in the mean SBP and DBP, respectively, from the baseline value after moxonidine treatment and during the follow-up with an additional reduction in body weight, plasma leptin levels and Body Mass Index (BMI) (p<0.01). Thus, moxonidine could be considered as a therapeutic option in obese patients with metabolic syndrome.

Management protocols for chronic heart failure in India

Heart failure is a common clinical syndrome and a global health priority. The burden of heart failure is increasing at an alarming rate worldwide as well as in India. Heart failure not only increases the risk of mortality, morbidity and worsens the patient’s quality of life, but also puts a huge burden on the overall healthcare system. The management of heart failure has evolved over the years with the advent of new drugs and devices. This document has been developed with an objective to provide standard management guidance and simple heart failure algorithms to aid Indian clinicians in their daily practice. It would also inform the clinicians on the latest evidence in heart failure and provide guidance to recognize and diagnose chronic heart failure early and optimize management.

M-shaped doppler signal across ventricular septal defect: potential implications for estimation of right ventricuilar systolic pressure.

An 8-year-old child suffering from ventricular septal defect and severe valvular pulmonary stenosis was evaluated by echo-Doppler technique and cardiac catheterization. A peak instantaneous transventricular systolic gradient of 64 mmHg was recorded across the ventricular septal defect with an interesting M-shaped spectral pattern. However, cardiac catheterization revealed a peak-to-peak non-simultaneous gradient between the right and the left ventricle of only 14 mmHg. This discrepancy along with its implications are discussed in this report.

Noncompaction of left ventricular myocardium in the presence of calcific aortic stenosis in an adult.

We describe an adult patient with a hitherto unreported association of severe aortic stenosis with extensive noncompaction of the left ventricular myocardium without any hypertrophy; however, there was severe left ventricular systolic dysfunction in the presence of a normal-sized left ventricular cavity on two-dimensional echocardiography. This condition was differentiated from persistence of embryonic intramyocardial sinusoids by selective coronary angiography.

Congenitally unguarded tricuspid valve orifice with a giant right atrium and a massive clot in an asymptomatic adult.

Congenitally unguarded tricuspid valve orifice, a variant of tricuspid valve dysplasia, is a rare malformation with protean manifestations. This report describes an asymptomatic adult who, on echocardiographic examination ordered in view of an abnormal 12-lead surface electrocardiogram and plain chest X-ray, was found to have an unguarded tricuspid valve orifice with a giant right atrium (12 x 10 cm), intense spontaneous echo contrast and a large right atrial clot.

Radiofrequency catheter ablation of common atrial flutter--acute and follow-up results.

Atrial flutter with a structurally well-defined macro-reentrant circuit in the right atrium has recently become amenable to radiofrequency ablation with the recognition of isthmus as a narrow zone of slow conduction. This study describes 20 consecutive and symptomatic patients with atrial flutter (15 males, 5 females; mean age 38.5 +/- 10.2 years) who underwent radiofrequency ablation in our institute in the last 18 months. Fourteen patients had structurally normal hearts, while the remaining six patients had specific disorders (prior surgery for closure of atrial septal defect-2, idiopathic restrictive cardiomyopathy-1, primary sinus node dysfunction-2, tachycardiomyopathy-1). The endpoints of a complete isthmus block and conversion to sinus rhythm were achieved in 19 of the 20 patients. Total number of pulses needed to attain the endpoints was a mean of 4.2 (range 1-5), each pulse being delivered for 90 seconds. At a mean follow up of 9.4 +/- 3.2 months (range 6-12 months), recurrence of atrial flutter was seen in one patient, atrial fibrillation in two and sinus node reentrant tachycardia in one. These results are comparable to those reported in the literature. Achievement of a complete isthmus block appears to be an important endpoint in obtaining optimal results. The issues of alternative sites of ablation, long-term results and advantages of an 8 mm tip catheter need to be examined further. In conclusion, radiofrequency ablation appears to be the preferred mode of treatment for patients with atrial flutter with excellent short-term and mid-term results.

Emergency mitral valve replacement for traumatic mitral insufficiency following balloon mitral valvotomy: an early haemodynamic study.

Acute severe mitral insufficiency may occur during percutaneous transvenous balloon mitarl valvotomy. Urgent surgical intervention in the form of mitral valve repair or replacement may be necessary in these patients. The haemodynamic measurements at various stages in these patients were obtained and compared with those of patients undergoing elective mitral valve replacement for chronic mitral regurgitation. Between September 1995 and December 1947, urgent mitral valve replacement was performed in 14 patients out of a total of 1688 patients who underwent balloon mitral valvotomy. Haemodynamic measurements could be obtained in 7 of these patients and they constituted group I. Eight other patients undergoing elective mitral valve replacement during the same period for chronic mitral regurgitation constituted group II. Standard haemodynamic measurements were obtained at the following stages: (1) Baseline- 20-30 min after endotracheal intubation; (2) stage 1- 20-30 min after termination of the cardiopulmonary bypass: (3) stage 2- four hours after the patient was transferred to ICU and (4) stage 3-30 min after extubation. All the patients were suffering from severe pulmonary hypertension. However, the indices of pulmonary artery hypertension such as mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance as well as right ventricular systolic and end-diastolic pressures did not decrease after surgery in group I. In contrast, in group II, there was significant decrease in mean pulmonary artery pressure (p<0.05), pulmonary capillary wedge pressure (p<0.05), right ventricular systolic (p<0.001) and end-diastolic pressures (p<0.05) at stage 1. These changes persisted throughout the study period. Pulmonary vascular resistance showed a decreasing trend, but attained statistical significance at stage 1 only. Two patients died; one of intractable cardiac failure and another from septicaemia and multiple organ failure in group I, but there were no deaths in group II. Reactive pulmonary hypertension secondary to acute mitral regurgitation may not recover immediately following mitral valve replacement and may be responsible for poor outcome in these patients.

Coronary artery stenting for isolated proximal left anterior descending stenosis: immediate and follow-up results.

Between February 1995 to August 1997, 120 patients underwent elective stent implantation for isolated proximal left anterior descending coronary artery stenosis. Their age ranged from 31 to 72 years (mean: 50.8 +/- 10.2) and the majority (89%) were males. All patients had angina, documented myocardial ischemia or both and 70 percent or more luminal diameter stenosis in the proximal left anterior descending before the origin of any branch. Majority (62.5%) of the treated lesions were type A. Successful deployment of the stent at the target site was achieved in all patients without any major in-hospital complications, including myocardial infarction, emergency bypass graft surgery or death. Clinical follow-up, ranging from 6 to 31 months (mean: 18.5 +/- 8.1, median: 20), was available in 87 out of 92 (94.5%) eligible patients who had completed at least six months after the procedure. Freedom from angina, myocardial infarction, target lesion revascularization and death was observed in 90.8, 100, 95.4 and 97.7 percent of patients, respectively. By the Kaplan-Meier estimate, an event-free survival (absence of death, myocardial infarction, recurrence of angina or revascularization) was 95.4 percent at six months, 89.5 percent at 12 and 18 months and 82.7 percent at 24 to 31 months of follow-up. Only 10 (11.5%) patients developed any event and TLR was required in 4.6 percent of patients. In conclusion, elective stenting for isolated proximal left anterior descending stenosis can be achieved safely and successfully in all patients without any adverse in-hospital events. This modality of treatment also provides long-term benefits in terms of reduction in major cardiovascular events and need for subsequent revascularization.

Age and intrinsic left ventricular myocardial contractility.

The purpose of this study was to compare the left ventricular (LV) intrinsic contractile function in normal elderly (age > or = 60 years, mean age 66 +/- 4 years) and young (age < or = 35 years, mean 27 +/- 9 years) healthy volunteers by stress-shortening and stress-length relationship using a co-variate analysis. Echocardiographically determined meridional and circumferential wall stress were plotted against LV fractional shortening, velocity of circumferential fibre shortening, end-systolic volume and diameter. LV ejection fraction, preload (denoted by end-diastolic volume) and afterload (expressed as circumferential wall stress) were similar in the two groups. Stress-shortening and stress-length relationships using the circumferential wall stress showed no difference in the two groups, although meridional wall stress was greater in the elderly population. Our results suggest that circumferential wall stress is a better method to detect intrinsic contractile abnormality in the elderly. Intrinsic LV ejection performance is within the normal range in the elderly healthy individuals.

Methodological variation and agreement in assessing mitral valve orifice area by echo-Doppler methods in mitral stenosis.

Two-dimensional echocardiographic planimetry of the directly observed mitral valve orifice, pressure-half-time methods, continuity equation and the Gorlin formula are commonly used to calculate the mitral valve area. However, there have been few comparisons of the four methods. In this study, the mitral valve orifice area was determined by the above four methods using echo-Doppler data in 49 consecutive patients in sinus rhythm (mean area 0.87 to 1.26 cm2). The valve area estimated by these methods correlated well (r = 0.7 to 0.97) with excellent agreement between the continuity equation and the Gorlin formula (mean difference 0.4 cm2, r = 0.97, SEE = 0.26) and between the planimetric area and the pressure-half-time method (mean difference = 0.06 cm2, r = 0.87, SEE = 0.23). However, the limits of agreement were wide and exceeded 1 cm2 in planimetry versus the Gorlin, planimetry versus the continuity equation and pressure-half-time method versus the Gorlin formula. The standard error of estimate varied from 0.23 to 0.51 cm2 for various comparisons. Use of an empirical constant of 51.6 instead of 37.7 in the Gorlin formula provided excellent correlation between the valve area determined by the continuity equation and the modified hydraulic formula (mean difference 0.07 cm2, r = 0.95, SEE = 0.08). Estimates of the valve orifice area by any of the equations tested should be seen as a guide rather than a precise measure of actual orifice area.

Comparative evaluation of left ventricular function in sick sinus syndrome on different long-term pacing modes.

Single-chamber ventricular pacing has been implicated in the development or progression of congestive heart failure in patients with sick sinus syndrome (SSS). To define the exact role of pacing modality in causation of congestive heart failure, quantitative two-dimensional echocardiographic examination was performed in 51 consecutive patients with SSS who received an initial pacemaker from January 1979 to September 1989 and were free of any structural heart disease at the time of implant. Atrial or dual chamber pacemakers were implanted in 21 patients (Group I) and ventricular pacemakers in 30 (Group II). The two groups were matched for age, gender, paced rate, blood pressure and duration of pacing. After a mean follow-up of 64 +/- 34 months, congestive heart failure developed in one patient in group I and 3 in Group II. Patients in group II, had larger left atrium (41 +/- 5 vs 37 +/- 6 mm, p < 0.05) and left ventricular end-diastolic volume (64 +/- 18 vs 54 +/- 12 ml/m2, p < 0.01) but similar left ventricular end-systolic volume (27 +/- 12 vs 24 +/- 9 ml/m2, p = NS), ejection fraction (59 +/- 10 vs 57 +/- 8%, p = NS), left ventricular mass (84.8 +/- 31 vs 85.6 +/- 29.2 gm/m2, p = NS), meridian end-systolic wall stress (48.3 +/- 22.1 vs 49.8 +/- 25 Kdynes/cm2, p = NS) and wall stress/end-systolic volume ratio (1.27 +/- 0.94 vs 1.42 +/- 0.59, p = NS). Pacing mode does not appear to influence left ventricular systolic function in patients with SSS.