The review deals with inflammation in heart failure (HF). Many data show that systemic inflammation is frequent in HF and implicate that inflammation contributes to damage and dysfunction of the cardiovascular system. Areas Covered: Experimental data have been mainly obtained in acute laboratory animal models. It is questionable whether animals' data can be translated into clinical settings with patients with chronic HF who have concomitant pathologies. The idea of a common inflammatory pathway that characterizes all different forms of clinical HF is unrealistic. It seems realistic that inflammation differs in non-cardiac and cardiac diseases. Research therapeutic options address the use of inhibitors of cytokines, of agents antagonizing oxidative stress, of MMP and of PI3K signaling pathways. Expert Opinion: Considering the many unknowns in our knowledge it is not surprising that early trials aimed to antagonize inflammation in HF have been disappointing. We are far away from having solid therapeutic schedules to use immunomodulation in all subtypes of HF. However, modern trials on HF due to virus infections have proven that immunomodulation is therapeutically effective. We should wisely use the known facts and accept that we have many unknowns. By appropriate selection of the subtypes of HF we may be able to find the appropriate therapy against inflammation in HF.

A 68-year-old man had a cardiac syncope. He was known to have a long QT-interval and was treated with ivabradine for paroxysmal sinusal tachycardia. In the last 5 days, azithromycin had been prescribed for sinusitis. An electrocardiogram showed torsades de pointes (TdP). Azithromycin is known to prolong the QT-interval. Ivabradine does not affect the QT-interval but has a conditional risk of TdP when taken with other drugs that block its metabolic breakdown. This case presents the specific problem of a patient with long QT who received two medications, which may interact and prolong the QT.

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Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

1 Of 662 hypertensive patients originally selected for long-term treatment, 580 were evaluated after one year and 169 continued for a second year of treatment with guanfacine.2 There were 257 women (mean age 52.1 yr) and 323 men (mean age 51.7 yr) in the trial: 499 (86%) suffered from essential, 55 (9%) from renal, 22 (4%) from renovascular and 4 (1%) from other forms of hypertension; 200 (34%) were classified as having mild, 275 (47.5%) moderate and 101 (17.5%) severe hypertension. In four patients the degree of severity was not specified. Nearly 40% of all patients had signs of left ventricular hypertrophy, and in 71% a pathological ocular fundus was found; 72% had been pretreated with antihypertensive drugs, 56% suffered from a concomitant disease and 18% had signs of heart failure; 224 patients were classified as having a sedentary mode of life, 316 were moderate and 27 heavy physical workers. In 13 no classification was given. 3 Whenever possible, a wash-out period of 3 weeks with a placebo identical in appearance with the active drug was carried out at the beginning and at the end of the 12-month treatment period to establish the pretreatment blood pressure and the possible withdrawal phenomena after therapy discontinuation. At the beginning, two doses of guanfacine 1 mg were administered daily and the dose was successively increased. A diuretic was added if necessary. To non-responders, a /3-adrenoceptor-blocker or a vasodilator was given. 4 In all trial groups a statistically significant decrease in blood pressure was found. The average reduction in mean arterial pressure was 16% at the end of the first year and 17% at the end of the second year. Normalization of blood pressure was achieved in 54% of the patients at the end of the first year and in 66% after the second year of treatment.5 In patients with hypertension of a higher degree of severity, combined treatment was used more often and higher doses of guanfacine were administered; monotherapy was used predominantly in patients with mild to moderate hypertension. 6 The mean daily dose of guanfacine at the end of the first year was 3.4 mg for monotherapy and 6 mg for combined treatment. After 2 yr, these values were 3.2 mg and 5 mg, respectively. 7 With the once-daily and twice-daily dosage schedules the same antihypertensive effect as with the three times daily dose regimen was observed, with a higher normalization rate and fewer sideeffects. Moreover, the normalization rate was higher with doses up to 3 mg than with doses in the range 4-25 mg. This applied to both monotherapy and combined treatment. 8 It is suggested that low doses of guanfacine are more suitable for the treatment of patients with established but uncomplicated hypertension, because of the lack of peripheral z-mimetic effects is the lower dose range. In view of the relatively long half-life of guanfacine, it is recommended that the drug be given only once daily or at the most twice daily. 9 The ECG analysis after one year of treatment revealed signs of regression in left-ventricul...