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Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including: psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.

Objective To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension. Subjects and setting In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348). Methods The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. Results Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006). Conclusions The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.

Coronary artery disease (CAD) risk factors influence the hyperemic response in patients without coronary artery stenosis. The aim of this study was to evaluate the influence of risk factors on coronary flow reserve (CFR) estimated by 99mTc-sestamibi cardiac imaging in patients with 1-vessel CAD. Methods: Fortyeight patients with 1-vessel CAD were enrolled in the study. Systemic hypertension, hypercholesterolemia, diabetes mellitus, and cigarette smoking were considered CAD risk factors. Within 48 h, all patients underwent coronary angiography and regional CFR assessment by 99mTc-sestamibi imaging with dipyridamole (0.74 mg/kg of body weight). Eight patients had no risk factors, 14 had 1 risk factor, 18 had 2 risk factors, and 8 had 3 risk factors. Results: The mean CFR of the narrowed coronary vessel was 1.28 +/- 0.43 in the overall study population (1.52 +/- 0.30 in patients with 50%–70% stenosis and 0.94 0.75 in patients with 70% stenosis; P < 0.001). Two-factor ANOVA showed that the number of risk factors significantly affected CFR (P < 0.001) in patients with 50%–70% stenosis, whereas significance was only borderline in patients with >70% stenosis. Finally, a significant interaction among the degree of coronary artery stenosis, the number of risk factors, and the estimated CFR was found. Conclusion: CFR is inversely related to the number of conventional risk factors in patients with 1-vessel CAD and intermediate coronary artery stenosis, whereas this influence is less evident in patients with more severe stenosis.

The additional prognostic value of thallium imaging in patients who are capable of performing a maximal, symptom-limited electrocardiographic stress test is still uncertain. Thus, we evaluated the incremental prognostic value of exercise thallium-201 indexes of myocardial hypoperfusion in 296 patients with suspected or known coronary artery disease who performed a maximal ECG stress test. At 2 year follow-up 20 hard events (16 cardiac deaths and 4 non fatal myocardial infarctions) and 44 soft events (myocardial revascularization procedures) occurred. Considering total events, thallium imaging provided significant additional prognostic information to clinical and exercise stress test data in all patients (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, whichever the end-point considered, thallium imaging did not add incremental prognostic value. When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give incremental prognostic information in patients with previous myocardial infarction but not in the subset of patients without previous infarction.

BACKGROUND: Cardiovascular disease is the most frequent cause of death of patients with acromegaly. AIM: To investigate whether young patients with a presumed short disease duration are more likely to reverse the acromegalic cardiomyopathy than older patients with longer disease duration. DESIGN: An open prospective design. PATIENTS: Ten young (aged < 40 years), and 12 middle-aged (41-59 years) patients with active acromegaly well controlled after 12 months of treatment with the depot formulation of octreotide (OCT-LAR); 22 sex- and age-matched healthy subjects as controls. METHODS: Left ventricular (LV) mass (LVM) by echocardiography and performance by equilibrium radionuclide angiography were measured before and after 12 months of OCT-LAR treatment. RESULTS: At study entry, none of the controls and 14 patients (63.4%) of whom six were young (chi2 = 17.7; P < 0.0001) had LV hypertrophy (LVH); none of the controls and four patients of whom one was young had insufficient LV ejection fraction (LVEF) at rest (< 50%); one control and 13 patients (59.1%) of whom five were young (chi2 = 12.7; P < 0.0001) had inadequate LVEF at peak exercise (deltaLVEF; < 5% increase of baseline). After 12 months, no change in haemodynamic and diastolic parameters was observed in both groups, except for a significant decrease in heart rate at peak exercise in young patients (P < 0.0001). The LVM index decreased significantly in both young (124.4 +/- 5.8 vs. 103.4 +/- 3.9 g/m2; P = 0.01) and middle-aged patients (140.9 +/- 7.9 vs. 117.8 +/- 6.6 g/m2; P = 0.03). LVH disappeared in 10 of 14 patients (71.4%): all six young and four of eight middle-aged patients (50%). LVEF at rest and at peak exercise increased significantly in both groups but deltaLVEF increased significantly only in young patients (1.5 +/- 2.9 vs. 13.7 +/- 5.2%, P = 0.04); it normalized in nine of 13 patients (69.2%), four of five young (80%) and four of eight middle-aged patients (50%). Exercise capacity (82.5 +/- 5.3 vs. 110.0 +/- 5.5 W, P = 0.005) and duration (7.3 +/- 0.3 vs. 9.9 +/- 0.4 min, P = 0.0003) also increased only in young patients. CONCLUSIONS: The acromegalic cardiomyopathy is reversed in most young patients with short disease duration and achieving disease control after OCT-LAR treatment for 12 months, indicating that early diagnosis and effective treatment are essential.

Gated SPECT allows combined assessment of regional myocardial perfusion and left ventricular function. The aim of this study was to address the prognostic value of gated SPECT performed during dobutamine stress testing and during rest on patients with acute myocardial infarction treated with thrombolysis. Methods: Eighty-eight consecutive patients with uncomplicated acute myocardial infarction who underwent predischarge (3-7 d after admission) dobutamine (5-40 mug/kg of body weight per minute in 3-min dose increments) and rest gated Tc-99m-sestamibi SPECT were followed for a mean of 48 mo (range, 4-64 mo). Results: Eighteen cardiac events (8 cardiac deaths and 10 nonfatal myocardial infarctions) occurred. Ischemia at dobutamine SPECT imaging (summed difference score 1) was present in 60% of the patients. In patients without ischemia, there was a lower event rate (11%), compared with patients with mild ischemia (18%) and moderate-to-severe ischemia (40%) (P < 0.05). Patients with events showed also a higher summed difference score, compared with patients without events (2.3 +/- 1.6 vs. 1.3 +/- 1.6, P < 0.05). Independent predictors of events were the number of segments with preserved 99mTc-sestamibi uptake at rest and the number of akinetic or clyskinetic segments with preserved Tc-99m-sestamibi uptake and preserved wall thickening (global chi(2) of the model, 13.6; P < 0.01). The assessment of the incremental prognostic value of variables added sequentially showed that the addition of the summed difference score added information to perfusion status at rest (P < 0.05). Combined assessment of regional myocardial perfusion and left ventricular function at rest further improved the model (P < 0.05). Conclusion: The present study indicated that predischarge Tc-99m-sestamibi gated SPECT gives prognostic information on patients recovering from acute myocardial infarction. Patients with preserved systolic wall thickening should be regarded as a high-risk subgroup, requiring closer follow-up for appropriate treatment.

This study evaluated the incremental prognostic value of 201TI reinjection imaging over clinical, exercise and thallium stress-redistribution data in patients with previous myocardial infarction and left ventricular dysfunction. METHODS: Thallium-201 reinjection after stress-redistribution SPECT was performed in 104 consecutive patients with a first Q-wave myocardial infarction (> 8 wk) and left ventricular ejection fraction < or = 40%. Follow-up data (mean 22 mo) were available for 98 patients; 16 patients underwent early revascularization procedures within 3 mo after exercise testing and were not considered for the analysis. RESULTS: During follow-up there were 13 hard events (cardiac death and myocardial infarction) and 11 soft events (coronary revascularization procedures > 3 mo after thallium imaging). With multivariate Cox regression analysis, the sum of defects at stress-redistribution imaging that were reversible or moderate irreversible after reinjection was a powerful predictor of subsequent events. The addition of thallium reinjection imaging data significantly improved the prognostic power of clinical, exercise and stress-redistribution data for the occurrence of hard events (p < 0.01). CONCLUSION: In patients with previous myocardial infarction and left ventricular dysfunction, thallium reinjection imaging provides incremental prognostic information over those obtained from conventional stress-redistribution imaging.

Large randomised trials have demonstrated that fibrinolytic therapy can reduce mortality in patients with suspected acute myocardial infarction (AMI). The indications for, and contraindications to, this treatment in some categories of patient are disputed, examples being late presentation, elderly patients, and those in cardiogenic shock. This overview aims to help resolve some of the remaining uncertainties. From all trials of fibrinolytic therapy versus control that randomised more than 1000 patients with suspected AMI, information was sought and checked on deaths during the first 5 weeks and on major adverse events occurring during hospitalisation. The nine trials included 58,600 patients, among whom 6177 (10.5%) deaths, 564 (1.0%) strokes, and 436 (0.7%) major non-cerebral bleeds were reported. Fibrinolytic therapy was associated with an excess of deaths during days 0-1 (especially among patients presenting more than 12 h after symptom onset, and in the elderly) but this was outweighed by a much larger benefit during days 2-35. This "early hazard" should not obscure the very clear overall survival advantage that is produced by fibrinolytic therapy. Benefit was observed among patients presenting with ST elevation or bundle-branch block (BBB)--irrespective of age, sex, blood pressure, heart rate, or previous history of myocardial infarction or diabetes--and was greater the earlier treatment began. Among the 45,000 patients presenting with ST elevation or BBB the relation between benefit and delay from symptom onset indicated highly significant absolute mortality reductions of about 30 per 1000 for those presenting within 0-6 h and of about 20 per 1000 for those presenting 7-12 h from onset, and a statistically uncertain benefit of about 10 per 1000 for those presenting at 13-18 h (with more randomised evidence needed in this latter group to assess reliably the net effects of treatment). Fibrinolytic therapy was associated with about 4 extra strokes per 1000 during days 0-1: of these, 2 were associated with early death and so were already accounted for in the overall mortality reduction, 1 was moderately or severely disabling, and 1 was not. This overview indicates that fibrinolytic therapy is beneficial in a much wider range of patients than is currently given such treatment routinely.

Twenty-four hour ambulatory blood pressure and electrocardiographic monitoring (Oxford method) was carried out in baseline conditions and after 15 days of therapy with a once a day administration of 240 mg verapamil slow-release in 11 elderly hypertensive patients. The 24 hour electrocardiographic monitoring (but not the blood pressure monitoring) was also carried out after 30 days of therapy. High-pressure liquid chromatography plasma concentrations of verapamil and its metabolite norverapamil were compared with the blood pressure and electrocardiographic responses. Systolic and diastolic blood pressure were significantly reduced after 15 days of therapy without circadian rhythm modification; mean heart rate was reduced after 15 and 30 days and the P-Q interval prolonged. Peak verapamil and norverapamil plasma concentrations were observed 8 hours after administration; at the 25th hour, the concentrations were respectively 60.9% and 68.3% of peak value (139.5 +/- 95.4 ng/ml and 126.4 +/- 60.9 ng/ml). Plasma levels of verapamil and norverapamil significantly correlated with heart-rate decrease. No correlation was observed between drug concentrations and systolic and diastolic blood pressure. A first-degree atrioventricular block was observed in 3 patients during therapy. Supraventricular premature contractions showed a decrease after 15 and 30 days of therapy. Thus, once a day administration of verapamil slow release is an effective anti-hypertensive medication in elderly hypertensive patients. Caution should be exercised in patients with P-Q interval prolongation and sinus bradycardia.

This study was undertaken in order to assess the K+ sparing ability of amiloride. Thirty patients with liver cirrhosis and ascites or congestive heart failure were divided into three groups and treated with amiloride (Group A), hydrochlorothiazide (Group B) and amiloride plus hydrochlorothiazide (Group C) for 15 days. In all groups there was an increased diuresis while only in group A and C there was a statistically significant rise of K+ serum levels and a slight increment of K+ urinary loss. Total body K+ evaluated by 42K increased in group A and C while decreased in group B. Our results seem to confirm that amiloride has a mild diuretic action with a powerful K+ sparing capacity; amiloride is also able to counterbalance and reverse hydrochlorthiazide induced K+ urinary loss.