Background: Dyspnea is a common symptom in a patient with valvular heart disease. The mechanism underlying this is still uncertain. Methods: We prospectively studied 20 patients with rheumatic mitral valve stenosis who were candidates for percutaneous balloon mitral valvotomy. Assessment of airway hyper-reactivity by histamine challenge test was done on all patients at baseline and at 1 week after the procedure. The provocative concentration of histamine solution required producing a 20% fall in forced expiratory volume in 1 second (FEV₁) (PC20) was recorded as a measure of airway hyper-reactivity. The severity of dyspnea in study subjects was also studied by the 6-minute-walk test and visual analog scale. Results: After balloon valvotomy, a significant improvement was seen in the six minute walking distance (219 ± 30.15 to 237.55 ± 32.25; p < 0.001), visual analog scale as a measure of dyspnea (60.95 ± 12.16 to 44.4 ± 13.71; p < 0.001) and airway hyper-reactivity (PC20; 5.69 ± 6.01 mg/ml to 10.16 ± 7.93; p < 0.001). Conclusions: Improvement in dyspnea in mitral stenosis after balloon valvotomy is associated with significant improvement in airway hyper-reactivity.

The long history of the beta-adrenergic receptor blockers for the treatment of hypertension is fraught with many controversies. The first compound had severe untoward effects preventing their use until propranolol was introduced. It was found effective for treatment of angina pectoris since not all patients with hypertension responded to monotherapy with a meaningful reduction of pressure. Nevertheless, the beta-blockers were most effective in: younger patients, especially with hyperkinetic circulation; with co-morbid diseases (e.g. coronary arterial disease with or without prior myocardial infarction); or when used with a diuretic. Subsequently with the advent of meta-analysis to evaluate more generalized experience, controversy resumed with statements made to exclude beta-blockers for initial hypertensive therapy. Support for this argument was gained with reports of patients developing ‘dysglycemia' with treatment. However, exclusion of any one therapeutic class for a multifactorial disease such as hypertension seems unrealistic. Meta-analysis confounded this conclusion since inadequate numbers of patients having specific clinical and biological characteristics were included (especially young patients). This is particularly important at this time when third-party reimbursement procedures are particularly relevant and when the primary care physician must deal with the individual patient. The NICE report has introduced specific thinking along these lines. In-and-of itself, its recommendations are reasonable, but current articles continue to suggest that the ‘older' beta-blockers should be excluded from national guidelines for initial antihypertensive therapy. Personally, I disagree; and, no doubt, controversy will continue.

Background: Atherosclerosis is considered to be an inflammatory disease. Infections are a significant cause of inflammation. Acute infections might precipitate acute coronary syndromes (ACS) whereas chronic infections might be stimuli for the development of atherosclerosis. Methods: Coronary angiograms were done on 211 of 335 patients with ACS and the percentage of coronary obstruction was determined. Serum antibody levels to Chlamydia pneumoniae, C. pneumoniae heat shock protein 60 (CpnHSP60), human heat shock protein 60 (hHSP60), enterovirus (EV), herpes simplex virus (HSV), cytomegalovirus (CMV), and two major periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were measured in healthy controls (n = 355) and all patients. Results: Serum antibody levels to periodontal pathogens did not correlate with ACS. However, IgA-class antibody levels to Aggregatibacter actinomycetemcomitans (p = 0.021), CpnHSP60 (p = 0.048) an hHSP60 (p = 0.038) were higher in patients with coronary occlusion or obstruction compared to those without any obstruction. Odds ratios for coronary changes in the highest quartile as compared to the lower quartiles were for A. actinomycetemcomitans IgA 7.84 (95% CI 1.02–60.39, p = 0.048), for CpnHSP60 IgA 8.61 (1.12–65.89, p = 0.038), and for human HSP60 IgA 3.51 (0.79–15.69, p = 0.100). Conclusions: We have previously reported that EV and HSV titres correlated significantly to acute coronary events. They do not correlate to the degree of coronary obstruction as shown here. However, infection by A. actinomycetemcomitans or C. pneumoniae or host response against them associated with coronary obstruction. Clinical coronary events may arise by the effect of acute infections and obstructing lesions by a chronic inflammatory stimulus.

Background: Microvascular and endothelial dysfunction have been implicated for coronary slow flow (CSF). Nebivolol, besides its beta-receptor blocking activity, causes an endothelium-dependent vasodilatation through increased nitric oxide release. Methods: This study included 27 patients with CSF and 27 subjects with normal coronary arteries. Segmental functions of the left ventricle (LV) were assessed using myocardial tissue Doppler velocities before and 3 months after treatment with nebivolol 5 mg/day. Results: Compared with the control group, mitral deceleration time (DT) was significantly longer, and E/A ratio, systolic velocity of lateral mitral annulus (S_m) and regional myocardial peak systolic and early diastolic velocities (V_s, V_d) were significantly lower in patients with CSF. The reason for coronary angiography was typical angina in 21 (77.8%) and positive treadmill test in six (22.2%) CSF patients. There were significant correlations between presence of CSF in left anterior descending artery (LAD) with S_m (r = -0.404, p = 0.002) and V_s in anterior (r = -0.531, p < 0.001) and lateral (r = -0.495, p < 0.001) segments and between presence of CSF in RCA and V_s in posterior segments (r = -0.501, p < 0.001). Treatment with nebivolol significantly decreased blood pressures (128.5 ± 12.5/82.5 ± 8.8 to 119.8 ± 12.6/76.4 ± 7.4 mmHg, p < 0.001), DT (252.3 ± 53.6 to 222.0 ± 41.0 ms, p < 0.001) and IVRT (115.7 ± 19.9 to 103.3 ± 17.0 ms, p < 0.001), and increased exercise capacity (8.7 ± 1.3 to 10.4 ± 0.9 METs, p < 0.001), E/A ratio (0.87 ± 0.26 to 1.08 ± 0.23, p < 0.001) and myocardial velocities (p < 0.001). All the patients were free of angina after treatment. Patients with CSF had impaired diastolic and regional LV functions. Conclusions: Nebivolol may therefore be useful in improving angina, exercise capacity and LV functions in patients with CSF.

Coronary heart disease is the leading cause of death in the Western world. Antithrombotic therapy is the cornerstone of its successful treatment. Clinical trials have demonstrated that antithrombotic therapy reduces the risk for recurrent myocardial infarction and cardiovascular death. Antiplatelet drugs and anticoagulants interfere with haemostasis and thus bleeding is a major risk factor of these drugs. The benefit of antithrombotic therapy must therefore be carefully balanced with the risk of bleeding and other potential adverse reactions of these drugs. However, to date there is no firm evidence that dosage adaptation of aspirin or clopidogrel according to platelet aggregation testing translates directly into any clinical benefit. Resistance to antithrombotic drugs is a serious problem because these patients are at a higher risk of myocardial infarction, stroke and cardiovascular death. It has most recently been demonstrated that resistance to clopidogrel is at least in part caused by polymorphism of CYP2C19. Clinical trials have also demonstrated that optimal benefit in different settings depends unequivocally on the meticulous choice of the various drugs. Thus, profound knowledge of the clinical pharmacological profiles of the different antithrombotic drugs is indispensable for successful treatment.

Bradyarrhythmias are common and may be caused by sinus node dysfunction or conduction block. Many of these conditions can be treated by the implantation of electronic cardiac pacemakers that reduce mortality and morbidity in carefully selected patient groups. Implantable electronic pacemakers are small, sophisticated and reliable but not without complication and limitation. Efforts have been made to create a de novo sinus node using gene therapy, the so-called biopacemaker. This approach has potential as permanent cure for bradyarrythmias with greater physiological responsiveness than that provided by rate-responsive electronic pacemakers. This article reviews the current approaches to the problem and gives a perspective on the challenges remaining to bring the therapy to clinical practice.

Background: Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown. Methods: EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF ≥ 50%). Patients were randomized to one of two treatment strategies, targeting systolic blood pressure (SBP) <140 mmHg or <130 mmHg using a combination of amlodipine/valsartan with additional antihypertensive medications as needed to achieve the prescribed targets. Diastolic function was assessed using Doppler tissue imaging of early diastolic velocity of lateral mitral annulus (E'), while vascular stiffness was assessed using radial augmentation index (RAI) derived from radial artery tonometry. The study primary endpoint will be the change in lateral E' velocity between baseline and 24 weeks. Results: Two hundred and twenty eight patients (50% female) with mean age of (59.6 ± 9.7) years and mean BP of (162 ± 14/92 ± 13 mmHg) were randomized equally to either treatment strategies. Left ventricular hypertrophy was present among <4% of the enrolled patients. Inspite diastolic function was impaired, baseline lateral E' velocity (7.6 ± 1.2 cm/s) was not related to baseline SBP while baseline RAI was weakly related (r = 0.2, p < 0.01) to SBP even after adjustment to age, gender and heart rate. Conclusion: EXCEED will determine whether intensive BP lowering will further improve diastolic dysfunction and vascular stiffness among patients with uncontrolled hypertension.