Clozapine induced myocarditis: a rare but fatal complication.

The need to consider myocarditis as one cause of flu-like symptoms in patients taking clozapine should be well entrenched. Suspicion should be heightened if the symptoms develop during the first 6-8 weeks of therapy. The FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. We aim to highlight the side effects of clozapine and increase awareness of this condition associated with the usage of the drug.

Lercanidipine vs lacidipine in isolated systolic hypertension.

This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.

Role of ambulatory blood pressure monitoring in the assessment and prognosis of patients with borderline hypertension.

The role of ambulatory blood pressure (ABP) monitoring in the assessment of mild/borderline hypertension (BHT) is unclear. The aim of this study was to test the hypothesis that measurement of ABP in borderline hypertensives differentiates patients with true mild hypertension from those with isolated clinic hypertension (raised office BP but normal ABP) and that a raised ABP identifies a subgroup who are more likely to progress to and require treatment over 1 year. Consecutive untreated patients with BHT (n = 127, 44 +/- 13 years, 45% male) were divided into two groups according to awake ABP: Group 1 (normal ABP < or = 136/86, n = 48), and Group 2 (abnormal ABP > 136/86, n = 79). Left ventricular mass index (LVMI) was greater (116 +/- 30 vs 101 +/- 25 g/m2, p < 0.01) and the proportion of patients with an increased LVMI was significantly higher (34% vs 17%, p = 0.05) in Group 2. During 1 year of follow-up, significantly more patients in Group 2 (34%) required antihypertensive treatment compared with Group 1 (8%, p = 0.01). ABP monitoring usefully discriminates between patients with true BHT and those with isolated clinic hypertension. An elevated awake ABP on initial assessment is associated with a higher LVMI and a greater likelihood of progression to moderate hypertension requiring pharmacological treatment.

Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects.

An absent or diminished blood pressure (BP) fall during sleep (so-called "nondipping") has been associated with a higher risk of cardiovascular complications, but the long-term reproducibility of dipper status and the relationship between diurnal changes in BP and perceived sleep quality have not been previously documented in untreated hypertensive patients. Ambulatory BP (ABP) and dipping status were examined in 79 subjects (69 hypertensives and 10 normotensives) at 0, 6, and 12 months. Fifty-six percent of subjects had no change in their dipping status, the majority (53%) dipping normally on all three occasions. However, 44% of patients had variable dipping status, and normal nighttime dipping in BP was observed more often when patients perceived their sleep quality to be good during the period of ABP recording. These results highlight significant intrasubject variability in the diurnal fluctuations in ABP and dipper status, which may in part reflect day-to-day variations in sleep disturbance during ABP monitoring. Classifying hypertensive patients into dippers or nondippers on the basis of a single ABP recording is unreliable and potentially misleading.

Clinical implications of white coat hypertension: an ambulatory blood pressure monitoring study.

Within routine clinical practice, white coat hypertension (where blood pressure is persistently higher in the presence of the doctor or nurse but normal outside the medical setting) makes the diagnosis and management of hypertension difficult. There are conflicting data regarding the prevalence and significance of white coat hypertension. This study has used ambulatory blood pressure monitoring to detect the presence of white coat hypertension in 186 patients referred to an out-patient hypertension unit. The presence of white coat hypertension was defined as an average office blood pressure (measured on three occasions over a 2-month period) of >140/90 mm Hg and an ambulatory awake blood pressure < or = 136/86 mm Hg. The prevalence of white coat hypertension in those patients with borderline hypertension (diastolic blood pressure 90-99 mm Hg) and those with mild-to-moderate hypertension (diastolic blood pressure > or = 100 mm Hg) was determined. Echocardiography was used to assess left ventricular mass index in patients with and without white coat hypertension. The prevalence of white coat hypertension in the total group was 23%. However, the prevalence was higher (33%) in those patients with borderline hypertension compared to 9% of those patients with mild-to-moderate hypertension. There was a statistically significant increase in left ventricular mass index in patients with no evidence of white coat hypertension (125 gm/m2) compared to those with white coat hypertension (102 gm/m2). We conclude that, if office blood pressure is used to identify patients with hypertension who may require treatment, some patients will be incorrectly diagnosed and may be treated inappropriately. We recommend that ambulatory blood pressure monitoring is used in the routine assessment of all newly diagnosed hypertensive patients. Furthermore, we recommend echocardiography in patients with borderline hypertension as some will already have an increased left ventricular mass index.

Twenty-four hour ambulatory blood pressure: a sample from a normal British population.

The aims of this study were to determine 24 h blood pressure (BP) levels in a sample taken from a normal British population, and to investigate factors contributing to variation within the sample. Two hundred and eighty-two Caucasian subjects, with no known hypertension or cardiovascular disease were recruited from local light industry and a general practice population. Office and 24 h BPs were measured. The mean office BP was 120/75, ambulatory mean awake 115/72 and mean asleep 97/58 mm Hg. Males had a small but significantly higher mean office and awake BP but there were no differences in asleep BP. Multiple step-wise regression with age, gender, weight and height showed age to be the best predictor of variation in office BP and awake and asleep diastolic BP. However, age accounted for only a small amount of the variation and did not contribute towards the variation in systolic BP. The two standard deviation upper limits for this population for awake, asleep and overall BP were 136/86, 121/73 and 131/82 mm Hg, respectively. In conclusion, these data providing information on 24 h BP in a healthy British population may be of value in the clinical interpretation of 24 h ambulatory BP recordings in patients with suspected hypertension.

Reduction in treatment delay by paramedic ECG diagnosis of myocardial infarction with direct CCU admission.

OBJECTIVES: To establish the feasibility of training paramedics of diagnose acute myocardial infarction by ECG before hospital admission and whether direct paramedic coronary care admission, arranged by very high frequency (VHF) radio communication with the coronary care unit (CCU), would reduce delay of thrombolysis treatment. DESIGN: Prospective controlled study. SETTING: District general hospital CCU and a local district ambulance paramedic service. PATIENTS: 124 patients with ECG evidence of myocardial infarction or ischaemia admitted directly to the CCU by the paramedic service were compared with 123 patients admitted by the emergency department and subsequently transferred to the CCU. MAIN OUTCOME MEASURES: ECG diagnostic accuracy by paramedics, and interval durations for CCU admission and thrombolysis. RESULTS: ECG diagnostic accuracy by the paramedics was 87.5% in the training phase and 92% in admission. The total call to thrombolysis interval was reduced from 154 to 93 minutes and the "door to needle" interval was reduced from 97 to 37 minutes. CONCLUSIONS: Trained paramedics can reliably diagnose myocardial infarction by ECG. The use of a direct admission procedure, by a VHF radio link to the CCU, substantially reduces the time interval for thrombolytic treatment after acute myocardial infarction.

Review: calcium antagonists and diuretics; a useful combination in the management of hypertension?

The use of the combination of a calcium antagonist with a thiazide diuretic for the treatment of hypertension has been the subject of much debate over a number of years. Early studies, with few subjects, demonstrated little benefit, but more recent research using larger numbers of subjects has shown quite clear additional antihypertensive effects of this combination. Combination therapy has an important role in the treatment of patients who do not respond to monotherapy, and the combination of a calcium antagonist and thiazide diuretic may be useful in the successful treatment of these patients.

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension.

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.

Long-term evaluation of treatment for chronic heart failure: a 1 year comparative trial of flosequinan and captopril.

Two hundred and nine patients with moderate to severe chronic heart failure, all of whom remained symptomatic despite at least 80 mg of frusemide daily, were randomized to 12 months treatment with flosequinan or captopril. The patients were stratified into two groups, a treadmill group and a corridor walk test group, depending upon their exercise capability. Sixty-five out of 102 patients randomized to flosequinan and 43 out of 107 randomized to captopril (p < 0.001) did not complete the study. There was no difference between the groups in mortality: 19 patients died while taking flosequinan and 15 while taking captopril. Both drugs had similar effects on treadmill exercise tolerance; the mean increase at week 52 was 117 seconds in the flosequinan group and 156 seconds (p = 0.57) for the captopril group. For those patients stratified to the corridor walk test only, there was also very little difference in the improvement at 52 weeks; the mean increase for patients randomized to flosequinan was 61 meters and captopril was 75 meters (p = 0.65). However, when the walk tests from all patients are examined, captopril produced a significant improvement compared with flosequinan at week 52 (p = 0.015). Flosequinan has similar long-term efficacy to captopril but is associated with a higher incidence of adverse events.

Raised ambulatory blood pressure in type 1 diabetes with incipient microalbuminuria.

Whether raised blood pressure precedes, follows or develops in parallel with the onset of microalbuminuria, remains unclear. Previous studies, using conventional blood pressure recordings, have yielded discrepant results. Ambulatory blood pressure (ABP) monitoring detects borderline hypertension more reliably, and correlates more closely with end-organ damage. We have therefore compared ABP and left ventricular dimensions in normotensive insulin-dependent diabetic patients with or without microalbuminuria, and matched nondiabetic control subjects. Those diabetic patients with microalbuminuria, and to a lesser extent those without, had higher 24 h mean arterial blood pressure than matched non-diabetic control subjects, with corresponding increases of left ventricular mass, interventricular septal width and posterior wall thickness. These observations suggest that raised arterial blood pressure is present at an early stage of 'incipient' microalbuminuria.

How reliable is the electrocardiogram in detecting left ventricular hypertrophy in hypertension?

This paper assesses the sensitivity and specificity of the electrocardiogram in detecting left ventricular hypertrophy in 75 hypertensive patients. Each patient underwent a 12 lead electrocardiogram and echocardiogram. Left ventricular mass index, using echocardiogram, was calculated according to the Penn convention and left ventricular hypertrophy was assessed by standard electrocardiographic criteria. The electrocardiogram was found to be very specific but insensitive in the detection of left ventricular hypertrophy as compared with the echocardiogram. Other non-voltage dependent markers appeared to have similar reliability. We conclude that the electrocardiogram may be unreliable in the detection of left ventricular hypertrophy in hypertensive patients. Accurate assessment of left ventricular hypertrophy, in these patients should be by echocardiography.

Type III collagen mutations cause fragile cerebral arteries.

Premature vascular aneurysms and fragility of cerebral arteries are commonly associated with type III collagen mutations and physical signs suggesting a generalized abnormality of connective tissue. Sometimes these traits are clearly genetically transmitted. Here we present seven examples of early cerebrovascular aneurysms or fragility including five examples of carotid cavernous sinus aneurysms. With one exception in which we suspect the mutation is too small to be detected, all of them had easily visible abnormalities of their type III collagen proteins. Further work in progress will eventually allow the characterization of their mutations at gene sequence level and will be followed by the ability to prevent transmission of the mutant genes in these families.

Echocardiographic demonstration of Escherichia coli endocarditis restricted to the pulmonary valve.

A 25 year old man with no history of heart disease presented with sweats and rigors. Echocardiography showed a large vegetation on the pulmonary valve and blood cultures grew Escherichia coli. Because of recurrent pulmonary emboli a large vegetation on the anterior leaflet of the pulmonary valve was excised. He recovered after a full course of antibiotics.

Prediction of "critical" coronary disease: are the "Consensus Conference" guidelines adequate?

Presenting features of 100 patients with significant left main coronary stenosis (LMCS) were reviewed. All presented with angina--on minimal exertion in 45, moderate exertion in 38, and severe exertion in 6--and 11 had unstable angina. Although the resting ECG was normal in 44, exercise testing was positive in 92% of patients tested. The authors conclude that symptoms and the resting ECG alone are unhelpful in predicting "critical" coronary disease. However, application of a management plan similar to that suggested by the Consensus Conference on coronary artery surgery would have selected the vast majority of such patients for angiography.