GUARD During Ischemia Against Necrosis (GUARDIAN) trial in acute coronary syndromes.

The plasma membrane sodium-hydrogen exchange system plays a major role in the pathophysiology of myocardial ischemia and reperfusion injury. The GUARD During Ischemia Against Necrosis (GUARDIAN) trial was undertaken to assess the potential clinical benefits of cariporide, a novel inhibitor of the sodium-hydrogen exchanger, in patients with acute coronary syndromes at risk of myocardial necrosis. This prospective, doubleblind, randomized, multicenter trial enrolled 11,733 patients who had unstable angina/non-Q-wave myocardial infarction (MI), or who required high-risk percutaneous interventions or coronary bypass surgery. Strict entry criteria were applied to ensure the enrollment of a population at high risk of developing complications. The patients were randomized to receive intravenous cariporide 20, 80, or 120 mg every 8 hours or placebo every 8 hours. Treatment was applied for the period of risk between 48 hours and 7 days. The primary efficacy endpoint was a composite of all-cause mortality and MI at 36 days. Secondary endpoints included the occurrence of the composite endpoint at day 10, events related to left ventricular dysfunction at day 36 and 6 months, extent of infarction, and refractory ischemia at day 36. Enrollment was completed in August 1998, and the results were presented at the American College of Cardiology meeting in New Orleans, Louisiana, USA, in March 1999.

The management of heart failure in Sweden.

Heart failure is a major concern to health care providers in Sweden due to its increasing prevalence and the rising health care costs. Heart failure affects more than 160000 Swedes, approximately 2% of the population. The costs for the management of heart failure have been calculated to be approximately SEK 2.500 million (Euro 275 million) which is 2% of the total health care budget. Most heart failure patients are managed by primary care physicians but hospitalisation is common and heart failure is the most common cause for hospitalisation in patients over 65 years of age. National diagnostic and treatment guidelines are not completely adhered to. Echocardiography is performed in a little more than 30% of patients in primary care probably due to poor access. In hospitals echocardiography is more easily available and routinely used for diagnosis. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers appear to be under prescribed. Nurse-led heart failure clinics are being widely established in an attempt to curtail costs and improve management.

Non-compliance and knowledge of prescribed medication in elderly patients with heart failure.

AIMS: To determine the extent of non-compliance to prescribed medication in elderly patients with heart failure and to determine to what extent patients recall information given regarding their medication. METHODS AND RESULTS: Non-compliance and knowledge of prescribed medication was studied in 22 elderly heart failure patients [mean age 79 +/- 6 (range 70-97); 14 (64%) male], using in-depth interviews performed 30 days after having been prescribed medication. All patients received standardised verbal and written information regarding their medication. Only 12 (55%) patients could correctly name what medication had been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could not account for when the medication was to be taken, i.e. at what time of day and when in relation to meals the medication was to be taken. In the overall assessment six (27%) patients were found non-compliant and 16 (73%) patients were considered as possibly being compliant with their prescribed medication. CONCLUSIONS: Non-compliance was common in elderly heart failure patients, as were shortcomings in patients knowledge regarding prescribed medication, despite efforts to give adequate information. There exists a need for alternative strategies to improve compliance in these patients.

The essence of effective treatment and compliance is simplicity.

In recent years, several international bodies of experts have established extensive guidelines for the prevention and treatment of coronary heart disease (CHD) that clearly define the importance of altering patients' lifestyles and administering therapeutic agents that positively affect disease progression. However, surveys of actual clinical practice have revealed that many of the key recommendations within these guidelines are not being implemented. The causes of this current undertreatment of CHD, although complex and varied, can be tackled in two main ways: by increasing physician adherence to guideline recommendations and by increasing patient compliance to medication. Experience shows that the existence of guidelines is not enough to ensure that physicians consistently apply the messages they contain. Difficulties in extrapolating clinical trial data to their patients, insufficient knowledge of the disease area, time constraints, and economic issues are a few examples of the barriers that may prevent physicians from achieving best practice. One way of addressing at least some of these problems may be to make greater use of nurses and other healthcare professionals, both in hospitals and in the primary care setting. Physicians must also be persuaded to employ long-term management and prevention strategies, as opposed to focusing on the short-term perspective. In doing so, the use of highly efficacious agents with a low incidence of associated adverse events will be the most successful in terms of maintaining patient compliance.

Cost effective management programme for heart failure reduces hospitalisation.

OBJECTIVE: To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure. DESIGN: Prospective, randomised trial. SETTING: University hospital with a primary catchment area of 250,000 inhabitants. PATIENTS: 190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure. INTERVENTION: Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice. MAIN OUTCOME MEASURES: Time to readmission, days in hospital, and health care costs during one year. RESULTS: The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07). CONCLUSIONS: A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.

Prognostic significance of changes in left ventricular systolic function in elderly patients with congestive heart failure.

BACKGROUND AND DESIGN: The prognostic significance of changes in left ventricular systolic function over time is unknown in elderly patients with heart failure. We prospectively examined the relation between 1-year changes in left ventricular systolic function by echocardiographic determination of atrioventricular plane displacement (AVPD), and subsequent 2-year mortality and morbidity in elderly patients with heart failure. AVPD determination allows for left ventricular function to be adequately assessed even when image quality is poor, as is common in the elderly. METHODS: AVPD was measured at baseline and 1 year in 123 patients with heart failure (age 76.0 +/- 5.4 years). An AVPD change of 1 mm or more (corresponding to an ejection fraction change of 0.05) was considered significant. RESULTS: AVPD decreased in 26 patients (21%), increased in 46 (37%), and was unchanged in 51 (42%). During a 2-year follow-up (from the 1-year examination) mortality, total hospitalizations, and hospitalizations for heart failure (35% of all hospitalizations) did not differ significantly between the three groups. Patients (n = 80) with AVPD of 8.2 mm or less (corresponding to left ventricular ejection fraction of 0.40 or less) at the 1-year examination demonstrated a higher mortality than patients with AVPD greater than 8.2 mm (43.8 versus 23.3%; P = 0.031), and also had more hospitalizations and days in hospital due to heart failure (1.0 +/- 1.5 versus 0.4 +/- 0.8, P = 0.020 and 10.4 +/- 15.6 versus 4.6 +/- 10.6, P = 0.033, respectively). CONCLUSIONS: Left ventricular function was readily assessed in all patients by determination of AVPD. Our results indicate that single but not serial assessment of left ventricular systolic function by determination of AVPD is of value in assessing the prognosis in elderly patients with heart failure.

A global survey of physicians' perceptions on cholesterol management: the From The Heart study.

AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.

A review of the current evidence for the use of angiotensin-receptor blockers in chronic heart failure.

Angiotensin-converting enzyme (ACE) inhibitors have a central role in the management of heart failure, reflecting the contribution of the renin-angiotensin-aldosterone system to the pathophysiology of the condition. Angiotensin-receptor blockers (ARBs) bind specifically to the angiotensin type 1 receptor and may offer further benefits compared with ACE inhibitors. Candesartan, losartan and valsartan have all been evaluated in large clinical outcome trials in heart failure. They display marked differences in pharmacokinetics and receptor-binding properties that may contribute to observed differences in outcome. ELITE II found no significant difference in outcome with losartan as compared with captopril. In the Val-Heft trial, valsartan reduced heart failure hospitalisations when added to conventional therapy including an ACE inhibitor in most patients, but had no effect on mortality. The CHARM programme showed that candesartan reduced morbidity and mortality in heart failure with reduced systolic function, both when added to ACE inhibitor therapy or when used as an alternative in patients who are intolerant to ACE inhibitors. Moreover, the CHARM-preserved study suggested that candesartan is beneficial in patients with heart failure and preserved left-ventricular systolic function. A growing body of evidence show that ARBs are an important contribution to the pharmaceutical management of patients with heart failure.

Endothelial dysfunction and cardiovascular disease: the promise of blocking the renin-angiotensin system.

As a crucial regulator of vascular function the endothelium balances a complex range of actions. Accordingly, damage to the endothelium often precedes the development of clinically manifest vascular disease. This review surveys our current understanding of risk factors involved in causing endothelial damage and the effects of lifestyle changes and pharmacotherapy on the endothelium. Our developing understanding of the intricacies of endothelial function and the effects of risk factors may aid in optimising cardiovascular prevention as well as therapy.

Right ventricular involvement in acute myocardial infarction.

Involvement of the RV in AMI is not as rare as previously thought and may lead to a particular clinical and hemodynamic syndrome with raised RV filling pressures, hypotension and oliguria. Major extension to the RV from inferior LV infarctions can be recognized by ST segment elevations iead CR4R or V4R. The significance of anterior RV extension and of RV papillary muscle infarction is still largerly unknown. It has been suggested from autopsy studies that the prognosis of patients with RV involvement might be poor healed extensive RV infarction is rarely seen. Indeed, ST segment elevation in lead CR4R indicating RV involvement has been found to carry a poor short-term prognosis. An increased awareness of the possibility of impaired RV function and of the special therapeutic considerations in some of these patients may increase survival.

Electrocardiographic changes in right ventricular infarction. A case report.

ST segment elevations in leads CR4R or V4R indicating right ventricular (RV) involvement are sometimes seen in patients with acute inferior transmural infarction. Whether the RV lesion per se or the concomitant infarction of the posterior septum causes this ECG pattern is unknown. We describe a patient with anteroseptal transmural infarction who developed unusually marked ST segment elevations in lead V4R. At autopsy, extensive old fibrotic infarction was found, involving the anterior and lateral RV walls, as well as recent necrosis of the interventricular septum. These findings suggest that the ST segment elevation in V4R in patients with RV infarction may not be caused by the RV necrosis per se but rather by visualization of the posterior septum through the necrotic RV myocardium.

Attempted diagnosis of ventricular mural thrombi in acute mycardial infarction using 125I-labelled fibrinogen.

In an attempt to diagnose ventricular mural thrombi complicating acute myocardial infarction (AMI), 80 patients have been given 100 muCi 125I-labelled fibrinogen after admission to a CCU. Precordial radioactivity was recorded for the following 6 days over four sites corresponding to chest leads CR1-CR4. A sustained rise in radioactivity of at least 15% of initial recordings was classed as type A pattern, a minor rise or flattened response as type B pattern and a rapid decrease as type C pattern; 28% showed a type A, 19% a type B and 54% a type C pattern. There was no significant difference between the groups in incidence of pericardial friction rub but when patients with suspected pericarditis (as evidenced by characteristic pains) were added, pericarditis was significantly overrepresented in the type A group. Smaller infarctions (SGOT less than 100 U/1) were significantly more common in patients with a type C decay pattern. No differences were noted between the groups as regards type and site of the infarction. A sustained rise in precordial radioactivity after an AMI may be an indication of mural thrombosis but the influence of other factors secondary to an infarction, e.g. pericarditis, cannot be determined at present.

Emergency room resuscitation of patients with cardiac arrest outside hospital. Outcome and immediate prognosis in 319 patients.

Resuscitation was attempted in 319 patients brought to hospital with cardiac arrest during a 5-year period. Primary successful results were achieved in 50 patients (15.7%). Twelve patients were long-term survivors (3.4%), 10 of whom had normal brain function, whereas 2 had mild cerebral dysfunction. To improve prognostication in patients with initially successful resuscitation, Bayes' theorem was applied using 4 clinical findings after 24 hours' treatment: reactions to painful stimuli, pupillary size, light reactions and BP, Bayes' theorem as well as coma depth after 24 hours gave valuable information regarding individual prognosis.