[Prognostic value of symptoms and signs of advanced heart failure and low left ventricle ejection fraction in patients after myocardial infarction with chronic heart failure]. / Wartosc rokownicza stopnia zaawansowania niewydolnosci serca i zmniejszonej frakcji wyrzutowej lewej komory u chorych na pozawalowa przewlekla niewydolnosc serca.

INTRODUCTION: Prognosis in patients (pts) after myocardial infarction (MI) with chronic heart failure (CHF) and asymptomatic left ventricular dysfunction (ALVD) differs. Acute coronary syndromes (ACS) worsen CHF and prognosis in these pts. A diagnostic tool that identifies the group of high risk pts is needed. Prognostic factors include left ventricle ejection fraction (LVEF) and stage of heart failure. The aim of the study was evaluation if decreased LVEF worsen prognosis in pts with CHF and ALVD and whether LVEF is more powerful predictor of poor prognosis than severity of heart failure. MATERIAL AND METHODS: 112 consecutive pts (95 men and 17 women age range 34-75, mean 52.9) post MI in stage B (ALVD) or stage C (CHF) according to ACC/AHA classification were studied. LVEF was determined in standard echocardiography with Simpson's method. Pts were divided into four groups: I--stage B and LVEF < or = 40% (6 pts); II--stage B and LVEF > 40% (52 pts); III--stage C and LVEF < or = 40% (19 pts); IV--stage C and LVEF > 40% (35 pts). The pts were followed for 30 months for the occurrence of the composite endpoint: major acute coronary events (MACE) i.e: ACS and cardiovascular deaths (CVD). In analysis we used chi2 test. RESULTS: There were 35 MACE during follow-up: 30 in pts in stage C and 5 in stage B. There were more MACE in group I than in group III (p < 0.01) and in group II than in group IV (p < 0.001). Pts in group I had more MACE than in group IV (p < 0.05). There were more MACE in group II than in group III (p < 0.01). Other results were not statistically significant. CONCLUSIONS: Stage of heart failure evaluated clinically is more powerful predictor of MACE than decreased LVEF. The more advanced stage of heart failure in post-MI pts, the higher risk of ACS or CVD. LVEF does not influence the risk of MACE in pts in the same stage of heart failure.

Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials.

BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.

Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina.

OBJECTIVES: The primary objective of the Monotherapy Assessment of Ranolazine In Stable Angina (MARISA) trial was to determine the dose-response relationship of ranolazine, a potentially new anti-anginal compound, on symptom-limited exercise duration. BACKGROUND: Fatty acids rise precipitously in response to stress, including acute myocardial ischemia. Ranolazine is believed to partially inhibit fatty acid oxidation, shift metabolism toward carbohydrate oxidation, and increase the efficiency of oxygen use. METHODS: Patients (n = 191) with angina-limited exercise discontinued anti-anginal medications and were randomized into a double-blind four-period crossover study of sustained-release ranolazine 500, 1,000, or 1,500 mg, or placebo, each administered twice daily for one week. Exercise testing was performed at the end of each treatment during both trough and peak ranolazine plasma concentrations. RESULTS: Exercise duration at trough increased with ranolazine 500, 1,000, and 1,500 mg twice daily by 94, 103, and 116 s, respectively, all greater (p < 0.005) than the 70-s increase on placebo. Dose-related increases in exercise duration at peak and in times to 1 mm ST-segment depression at trough and peak and to angina at trough and peak were also demonstrated (all p < 0.005). Ranolazine had negligible effects on heart rate and blood pressure. One year survival rate combining data from the MARISA trial and its open-label follow-on study was 96.3 +/- 1.7%. CONCLUSIONS: In chronic angina patients, ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinically meaningful hemodynamic effects. One-year survival was not lower than expected in this high-risk patient population. This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients.

Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.

CONTEXT: Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications. In a previous trial, antianginal monotherapy with ranolazine, a drug believed to partially inhibit fatty acid oxidation, increased treadmill exercise performance; however, its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina. OBJECTIVES: To determine whether, at trough levels, ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia, effect on angina attacks and nitroglycerin use, and effect on long-term survival in an open-label observational study extension. DESIGN, SETTING, AND PATIENTS: A randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating ambulatory outpatient settings in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and followed up through October 31, 2002. INTERVENTION: Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment. MAIN OUTCOME MEASURES: Change in exercise duration, time to onset of angina, time to onset of ischemia, nitroglycerin use, and number of angina attacks. RESULTS: Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups (pooled) vs 91.7 seconds in the placebo group (P =.01). The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups, at peak more than at trough. The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks. Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo (P<.02). Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4% in the first year and 95.9% in the second year. CONCLUSION: Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking standard doses of atenolol, amlodipine, or diltiazem, without evident adverse, long-term survival consequences over 1 to 2 years of therapy.

[Factors influencing cardiac complications in patients with type-2 diabetes mellitus and silent myocardial ischaemia: five-year follow-up]. / Co decyduje o wystepowaniu powiklan kardiologicznych u osób z cukrzyca typu 2 i niemym niedokrwieniem? piecioletnia obserwacja.

UNLABELLED: Silent myocardial ischaemia (SMI), a common disorder, has been studied by different research groups for the last 25 years. It is known that SMI is more common in patients with type 2 diabetes mellitus (type 2 DM) than in the general population, even though pathological mechanisms responsible for SMI are unclear. The aim of the study was to assess the role of SMI and other conditions in predicting adverse outcome in patients with type 2 DM during five years of follow-up. MATERIALS AND METHODS: 67 males with type 2 DM were enrolled into the study group. 55-healthy men were used as a control group (CG). Precise clinical examinations (medical history, physical examination, laboratory tests) were conducted. Coronary risk factors and the level of diabetes control were assessed. Noninvasive cardiological tests: ETT, 24 h ECG and echocardiography were performed. The prevalence of the following complications: ischaemia, unstable angina, myocardial infarction, heart failure, death and need for invasive procedures was recorded for five years. Parameters responsible for the complications were analyzed with the use of univariate logistic regression test; odds ratio was calculated. RESULTS: The silent myocardial ischaemia was found in 32.8% of patients with type 2 DM and in 9.1% men in control group (p < 0.001). The complications were observed in 24% of men with DM and in 16% in control group (NS). It was found that 25 parameters in the studied group and 16 parameters in the control group were statistically significant for the prediction of complications (among analyzed 92 parameters). The most important of them in type 2 DM group are: duration of diabetes (years) OR--1.18 (p < 0.01), fasting glucose (mg/dl) OR--1.017 (p < 0.01), SMI episodes (ETT) OR--4.72 (p < 0.01), diastolic dysfunction (E/A), OR--0.003 (p < 0.02) and left ventricle hypertrophy OR--3.86 (p < 0.05), whereas in CG--SMI episodes, OR--17.72 (p < 0.002). CONCLUSIONS: (1) The silent myocardial ischaemia is common in patients with type 2 DM. It was diagnosed in 33% of the patients. (2) The presence of SMI significantly increases the risk of complications both in patients with diabetes mellitus and the control group. (3) There are many other factors predisposing to the complications. In patients with diabetes mellitus they included, besides SMI, the duration of diabetes, chronic hyperglycemia and left ventricular diastolic dysfunction.

Calcium blocker therapy before myocardial infarction increases post-infarction short- and long-term mortality. Data from the INJECT trial.

BACKGROUND: Short-acting calcium channel blockers (Ca-blockers) have been shown in some studies to increase the risk of myocardial infarction (MI) and post-MI complications. Data from large, international, randomised studies such as the INJECT trial may bring new important information on the effects of medication used before MI, on the course of MI and post-MI complications. AIM: To assess the effects of beta-blocker and Ca-blocker therapy administered prior to MI on the early and late outcome after MI. METHODS: The study group consisted of 6001 patients with acute MI treated according to the INJECT protocol. The patients were divided into four groups according to the type of treatment before the index MI: Group I (n=580) - patients treated with beta-blockers; Group II (n=831) - patients treated with Ca-blockers; Group III (n=277) - patients treated with both beta-blockers and Ca-blockers; and Group IV (n=4313) - no beta-blocker or Ca-blocker treatment. The analysed end-points were 35- and 180-day mortality as well as angina recurrences, occurrence of heart failure, atrial fibrillation/flutter and asystole. RESULTS: During hospital stay, supraventricular arrhythmias, asystole, recurrent ischaemia and heart failure occurred more frequently in patients from groups II and III than in other groups. Early mortality was significantly higher in group II (p<0.001) and group III (p<0.002) than in group IV. Late mortality was the lowest in group IV, followed by group I. Cox proportional hazards multivariable analysis revealed that hypotension, Killip class IV (p<0.001), previous Ca-blocker (p<0.01) or Ca- and beta-blocker treatment (p<0.01) as well as previous MI (p<0.05) were the independent predictors of death. CONCLUSIONS: Compared with beta-blocker therapy or no treatment, previous use of Ca-blockers increases both early and long-term complication rates in patients with MI.