Incremental value of left ventricular systolic and diastolic function to determine outcome in patients with acute ST-segment elevation myocardial infarction: the echocardiographic substudy of the OASIS-6 trial.

BACKGROUND: The echocardiographic substudy of the OASIS-6 trial evaluated the prognostic implications of left ventricle (LV) systolic and diastolic dysfunction early postacute ST-segment elevation myocardial infarction (STEMI) in patients treated with fondaparinux versus usual care. METHODS: Comprehensive echocardiograms were performed a median of 6 days after the index STEMI in 528 patients, 258 randomized to fondaparinux and 270 to usual care (unfractionated heparin or placebo), to assess LV systolic and diastolic function, LV mass, and LV end-systolic and end-diastolic volumes. A total of 245 (46.4%) patients were followed up for 3 months and 283 (53.6%) for 6 months. Major cardiac events (MACE) were defined as the composite of death, reinfarction, heart failure, or cardiogenic shock and resuscitated cardiac arrest. RESULTS: Patients with LV ejection fraction (LVEF) ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of MACE (hazard ratio [HR] = 8.85, 95% CI, 4.21­18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR = 4.38, 95% CI, 1.52­12.60) and in multivariate models adjusted for LVEF, LV end-systolic volume, and clinical variables. CONCLUSION: In this large international trial, LV systolic and diastolic function, as determined by echocardiography early following STEMI, are incremental predictors of MACE. In addition, RDF is a strong independent predictor of MACE after STEMI across a broad range of LVEF.

Reversible pulmonary hypertension related to thalidomide treatment for multiple myeloma.

Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects. Thalidomide is an effective treatment; however, it has been associated with an increased risk of thromboembolic events including pulmonary hypertension (PH). PH in the absence of thromboembolic events has also been described in some patients with MM during thalidomide treatment. We experienced occurrence of PH in a MM patient during treatment with thalidomide. A 79-year-old woman was diagnosed with IgG lambda MM and was started on thalidomide treatment. About a month later, she presented with asthenia, palpitation and dyspnoea on exertion and was hospitalized. An echocardiography revealed severe PH (systolic pulmonary artery pressure 75 mm Hg) without paradoxic movement of ventricular septum or right ventricular dysfunction signs; a previous echocardiography was normal. Pulmonary computed tomography and perfusion scan were negative for pulmonary embolism. Based on the hypothesis of a pharmacological pathogenesis, thalidomide was promptly interrupted. About a month later, she was hospitalized for further investigations. Physical examination documented absence of dyspnoea or other respiratory signs, and echocardiography showed normal right ventricular function and normal pulmonary artery pressure. As in the cases reported in the literature, we suggest a possible direct correlation between thalidomide and PH, since in all cases a rapid decrease of pulmonary artery pressure after thalidomide discontinuation was observed.

Mesoangioblasts, vessel-associated multipotent stem cells, repair the infarcted heart by multiple cellular mechanisms: a comparison with bone marrow progenitors, fibroblasts, and endothelial cells.

OBJECTIVE: To test the potential of mesoangioblasts (Mabs) in reducing postischemic injury in comparison with bone marrow progenitor cells (BMPCs), fibroblasts (Fbs), and embryonic stem cell-derived endothelial cells (ECs), and to identify putative cellular protective mechanisms. METHODS AND RESULTS: Cells were injected percutaneously in the left ventricular (LV) chamber of C57BL/6 mice, 3 to 6 hours after coronary ligation, and detected in the hearts 2 days and 6 weeks later. Echocardiographic examinations were performed at 6 weeks. LV dilation was reduced and LV shortening fraction was improved with Mabs and BMPCs but not with ECs and Fbs. Donor cell colonization of the host myocardium was modest and predominantly in the smooth muscle layer of vessels. Capillary density was higher in the peripheral infarct area and apoptotic cardiomyocytes were fewer with Mabs and BMPCs. Mabs and BMPCs, but not Fbs or ECs, promoted survival of cultured cardiocytes under low-oxygen in culture. This activity was present in Mab-conditioned medium and could be replaced by a combination of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and hepatocyte growth factor (HGF), all of which are produced by these cells. Conditioned medium from Mabs, but not from Fbs, stimulated proliferation of smooth muscle cells in vitro. CONCLUSIONS: Mabs appear as effective as BMPCs in reducing postinfarction LV dysfunction, likely through production of antiapoptotic and angiogenic factors.

Eplerenone, a selective aldosterone blocker, improves diastolic function in aged rats with small-to-moderate myocardial infarction.

BACKGROUND: The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI. Methods and results Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9) given 18 days postsurgery and up to sacrifice 3 months later. At sacrifice, untreated MI rats did not show overt systolic dysfunction but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01) and in aorta (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial interstitial collagen and aortic fibrosis (all parameters statistically different from untreated MI). CONCLUSION: In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.

Low frequency spectral component of heart rate variability and myocardial beta-adrenoceptor density after acute myocardial infarction.

OBJECTIVE: The low frequency spectral component (LF; 0.04-0.15 Hz) of heart rate variability (HRV) is considered to be an index of sympathetic modulation of sinus node activity under physiological conditions, although the relationship is less clearly defined in non-physiological conditions. Several cardiovascular diseases are characterized by an absent or blunted 24-h pattern of the LF spectral component. The aim of the present study was to investigate the relationship between chronically increased neural sympathetic efferent drive to the heart, quantified in terms of downregulation of myocardial beta-receptors, and the 24-h power of the LF spectral component in patients after acute myocardial infarction. METHODS: In 24 patients, HRV was analyzed for a 24-h period, one month after an uncomplicated Q wave myocardial infarction. The following time domain measures and spectral components were calculated: mean RR, SDNN, SDANN, RMSSD, SDNN index, pNN50, and very low frequency (VLF), low frequency (LF) and high frequency (HF) spectral components. The density of beta-adrenoceptors was measured in vivo by positron emission tomography (PET) with 11-CGP-12177. RESULTS: Post-AMI patients had normal plasma levels of adrenaline and noradrenaline (respectively 1.48 +/- 0.18 and 0.28 +/- 0.03 IU/L) but reduced myocardial beta-adrenoceptor density (6.86 +/- 0.24 pmol/g). Patients had similar heart rates but lower values of SDNN and SDANN compared with control subjects. The absolute and normalized power of the spectral components were similar in the two groups, but the usual day-night oscillation was blunted in patients. Moreover, the day-night change in the power of the LF spectral component was positively related (r = 0.51; p < 0.001) to the myocardial beta-adrenoceptor density. CONCLUSIONS: The loss of the day-night oscillation of the LF spectral component appears to be a significant marker of sustained sympathetic over-activity in post-AMI patients.