Sustained quality of life improvement after intracoronary injection of autologous bone marrow cells in the setting of acute myocardial infarction: results from the BONAMI trial.

PURPOSE: Cardiac cell therapy is a promising treatment for acute myocardial infarction (AMI), leading to cardiac function improvement. However, whether it translates into quality of life (QoL) improvement is unclear. We hypothesized that administration of bone marrow cells (BMC) to patients with AMI improves QoL. METHODS: In the multicenter BONAMI trial (NCT00200707), patients with reperfused AMI and decreased myocardial viability were randomized to intracoronary autologous BMC infusion (n = 52) or state-of-the-art therapy (n = 49). QoL data, derived from the Minnesota Living with Heart Failure questionnaire (MLHFQ), were obtained 1, 3, and 12 months after AMI and analyzed using a Rasch-family model. RESULTS: Using this model, QoL improved over time in the BMC group (p = 0.025) but not in the control group. Furthermore, the BMC-group patients displayed a better QoL than the control-group patients at 3 and 12 months post-AMI (p = 0.034 and p = 0.003, respectively). These findings were not detected when analyzing MLHFQ data using a standard method. Cardiac function, myocardial viability, mortality, and number of major adverse cardiac events did not differ between treatment groups. CONCLUSION: Our results suggest that BMC therapy can improve QoL, stressing the need for confirmation trials and for systematic QoL assessment in cardiac cell therapy trials .

Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial.

PURPOSE: Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. METHODS: Patients with acute MI and ejection fraction (EF) ≤ 45 % were randomized to cell therapy or to control and underwent thallium single-photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. RESULTS: At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p < 0.001), without significant increase in LV mechanical dyssynchrony. During follow-up, there was a progressive increase in LV SD (p = 0.01). Baseline independent predictors of LV remodelling were perfusion SPECT defect size (p = 0.001), LVEF (p = 0.01) and a history of hypertension (p = 0.043). Bone marrow cell therapy did not affect the time-course of LV remodelling and dyssynchrony. CONCLUSIONS: LV remodelling 1 year after reperfused MI is associated with progressive LV dyssynchrony and is related to baseline infarct size and ejection fraction, without impact of cell therapy on this process.

Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study.

AIMS: To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real-life setting in France. METHODS AND RESULTS: We conducted an observational survey constituting a single-day snapshot of all unplanned hospitalizations because of AHF in 170 hospitals throughout France (the OFICA survey). A total of 1658 patients (median age 79 years, 55% male) were included. Family doctors were the first medical contact in 43% of cases, and patients were admitted through emergency departments in 64% of cases. Clinical scenarios were mainly acutely decompensated HF (48%) and acute pulmonary oedema (38%) with similar clinical and biological characteristics as well as outcome. Characteristics were different and severity higher in both shock and right HF. Infection and arrhythmia were the most frequent precipitating factors (27% and 24% of cases); diabetes and chronic pulmonary disease were the most frequent co-morbidities (31% and 21%). Over 80% of patients underwent both natriuretic peptide testing and echocardiography. LVEF was preserved (>50%) in 36% of patients and associated with specific characteristics and lower severity. Median hospital stay was 13 days; in-hospital mortality was 8.2%, and independent predictors were age, blood pressure, and creatinine. Treatment at discharge in patients with reduced LVEF included ACE inhibitors/ARBs, beta-blockers, and aldosterone inhibitors in 78, 67, and 27% cases. Non-surgical devices were reported in <20% of potential candidates. CONCLUSION: This comprehensive survey analysing AHF in real life emphasizes the heterogeneous nature and overall high severity of AHF. It could be a useful tool to identify unsolved medical issues and improve outcome. TRIAL REGISTRATION: NCT01080937.

Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial.

AIMS: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. METHODS AND RESULTS: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. CONCLUSION: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode.

AIMS: Whether or not beta-blocker therapy should be stopped during acutely decompensated heart failure (ADHF) is unsure. METHODS AND RESULTS: In a randomized, controlled, open labelled, non-inferiority trial, we compared beta-blockade continuation vs. discontinuation during ADHF in patients with LVEF below 40% previously receiving stable beta-blocker therapy. 169 patients were included, among which 147 were evaluable. Mean age was 72 +/- 12 years, 65% were males. After 3 days, 92.8% of patients pursuing beta-blockade improved for both dyspnoea and general well-being according to a physician blinded for therapy vs. 92.3% of patients stopping beta-blocker. This was the main endpoint and the upper limit for unilateral 95% CI (6.6%) is lower that of the predefined upper limit (12.5%), indicating non-inferiority. Similar findings were obtained at 8 days and when evaluation was made by the patient. Plasma BNP at Day 3, length of hospital stay, re-hospitalization rate, and death rate after 3 months were also similar. Beta-blocker therapy at 3 months was given to 90% of patients vs. 76% (P < 0.05). CONCLUSION: In conclusion, during ADHF, continuation of beta-blocker therapy is not associated with delayed or lesser improvement, but with a higher rate of chronic prescription of beta-blocker therapy after 3 months, the benefit of which is well established.

Candesartan cilexetil in the treatment of chronic heart failure.

The prevalence of heart failure is ever increasing around the world, particularly due to aging populations. Despite improvements in treatment over the last 20 years, the prognosis for heart failure remains poor. Among the treatments recommended for chronic heart failure, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are crucial, provided of course that they are not contraindicated. However, angiotensin II receptor blockers (ARBs) can also be a beneficial treatment option. Candesartan is a particular ARB, characterized by a strong binding affinity to the angiotensin II type 1 receptor and slow dissociation. The benefits of candesartan have been demonstrated by the CHARM programme, which showed that candesartan significantly reduces the incidence of cardiovascular death, hospital admissions for decompensated heart failure, and all-cause mortality in chronic heart failure patients with altered left ventricular systolic function, when added to standard therapies or as an alternative to ACE inhibitors when these are poorly tolerated. Furthermore, candesartan can protect against myocardial infarction, atrial fibrillation and diabetes. Tolerance to candesartan is good, but blood pressure and serum potassium and creatinine levels must be monitored.

Study of nycthemeral variations in blood pressure in patients with heart failure.

OBJECTIVE: The objective of this study was to describe and analyse the nycthemeral variations in blood pressure (BP) by ambulatory BP monitoring (ABPM) over 24 h in patients with heart failure (HF). METHODS: The study population included 50 stable HF patients hospitalized in a cardiology department for acute pulmonary oedema. Parameters studied were: New York Heart Association class, clinical resting BP and heart rate in sitting and then standing positions, ABPM parameters, distance covered during a 6-min walking test, echographic left ventricular ejection fraction (LVEF), natremia, kaliemia, creatininemia, plasma haemoglobin and N-terminal fragment of brain-type natriuretic peptide levels. RESULTS: Clinical hypertension was noted in 20% of patients (10/50) and orthostatic hypotension in 16% (8/50). Nine of 50 patients (18%) were hypertensive during the day and 21 (42%) at night. Thirty-nine of the 50 patients (78%) are nondippers. Nondipper patients are more prevalent when the HF has been present for more than 24 months (95 vs. 67%, P=0.04). This prevalence does not differ depending on New York Heart Association class or LVEF. Furthermore, there exists: (i) a significant positive relationship (R=0.46, P=0.02) between the diastolic BP (DBP) over 24 h and the distance covered during the walking test; (ii) a significant negative relationship between the day-night differences (in mmHg) of the systolic BP (SBP) (R=-0.46, P=0.01) and DBP (R=-0.33, P=0.03) and the duration of HF, between the day-night difference of the DBP and the LVEF (R=-0.34, P=0.02) and (iii) between the day-night differences of the SBP (R=-0.48, P=0.001) and the DBP (R=-0.32, P=0.03) and natremia. The day-night difference of the SBP has a positive correlation with plasma haemoglobin level (R=0.32, P=0.03). CONCLUSION: This study confirms the feasibility of carrying out ABPM with an adapted device in HF patients with atrial fibrillation. ABPM allows diagnosis to be more precise than the clinical measuring of BP abnormalities, which have a pejorative prognosis (e.g. hypertension, hypotension, nondipper status).

[Masked hypertension: myth or reality?]. / Hypertension artérielle masquée: mythe ou réalité.

Masked hypertension is also referred as reverse white coat hypertension. Masked hypertension is diagnosed in subjects who have normal clinic blood pressure (BP) <140/90 mmHg and elevated ambulatory BP or home BP, with daytime systolic BP> or = 135 mmHg or daytime diastolic BP > or = 85 mmHg. Its prevalence varies between 10 to at least 47% and differs substantially according to the reference population and the specific criteria.Subjects with masked hypertension have been shown to have more extensive target organ damage, specifically, a higher prevalence of carotid atherosclerosis and of left ventricular cardiac hypertrophy. Longitudinal studies of patients with masked hypertension show higher levels of cardiovascular morbidity and mortality than in reference populations. These studies show that ambulatory or home BP measurements predict risk much better than the usual clinical measurements and that those who are found to be hypertensive by ambulatory or home measurements have greater risks than those who are not. Who should be tested for masked hypertension? Our reference study shows that 3 characteristics are most likely to predict masked hypertension: male sex, age over 60 years, and office systolic BP of more than 130 mmHg. Masked hypertension is indeed a reality. Individual patients should be tested and treated, based on the physician's clinical judgment.

N-terminal pro-brain natriuretic peptide predicts myocardial ischemia and is related to postischemic left-ventricular dysfunction in patients with stable coronary artery disease.

BACKGROUND: The N-terminal-pro-B natriuretic peptide (Nt-pro-BNP) is of diagnostic and prognostic value in coronary artery disease (CAD). We assessed the relationship between Nt-pro-BNP and (1) the extent of ischemia on stress myocardial perfusion imaging (MPI), and (2) changes between the basal and postexercise ejection fraction (EF), in stable patients with a normal EF. METHODS AND RESULTS: One hundred and two patients with stable, documented CAD (EF, 62% +/- 8%) underwent an exercise-rest thallium-201 gated-MPI and serial Nt-pro-BNP assays. Myocardial perfusion imaging produced abnormal results in 57 patients (56%; group 1), and normal results in 45 patients (44%; group 2). Median baseline, immediate postexercise, and 3-hour postexercise Nt-pro-BNP values were higher in group 1 than in group 2: 182 vs 85, 201 vs 86, and 212 vs 99 pg/mL, respectively (P < .001 for all). Postexercise EF decreased in group 1 (53% +/- 11% vs 62% +/- 10%, P < .001), but not in group 2 (61% +/- 9% vs 62% +/- 7%, NS). The Nt-pro-BNP ruled out significant ischemia with a negative predictive value of 0.90, whereas patients within the higher tertile of Nt-pro-BNP had a fivefold higher risk of ischemia compared with patients within the lower tertile. CONCLUSIONS: The post-stress increase in Nt-pro-BNP is related to myocardial ischemia and to postischemic left-ventricular dysfunction, and accurately predicts the presence or absence of myocardial perfusion defects.

Validation of the AGILIS ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults.

BACKGROUND: We evaluated the clinical validity of the AGILIS ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol. METHODS: The blood pressure (BP) was measured at the same arm by two certified observers using two mercury columns and a double stethoscope, then by the volunteer with the automatic device, these measurements were done seven times sequentially using 33 volunteers. For the randomization of the patient, one ABPM measure was compared to the mean of three manual measures. Then, we had three ABPM measures and four manual measures. Each ABPM measure, being compared to two manual measures. Blood pressure readings and recordings were blinded. Position of the subjects was standardized. RESULTS: Phase 1: To pass phase 1, the device had to have at least 25 of the 45 measurements within 5 mmHg, 35 within 10 mmHg or 40 within 15 mmHg of the comparative observer measurements. The AGILIS monitor had 35 measurements lying within 5 mmHg, 42 within 10 mmHg and 45 within 15 mmHg for systolic BP (SBP), 35 within 5 mmHg, 44 within 10 mmHg and 45 within 15 mmHg for diastolic BP (DBP). It passed the criteria for SBP and DBP. Phase 2: To pass phase 2.1, a device must have at least 60 of 99 measurements within 5 mmHg, 75 within 10 mmHg and 90 within 15 mmHg of the comparative observer measurements, and in addition must also have either 65 within 5 mmHg and 80 within 10 mmHg, or 65 within 5 mmHg and 95 within 15 mmHg, or 80 within 10 mmHg and 95 within 15 mmHg. The AGILIS monitor had 78 measurements within 5 mmHg, 91 within 10 mmHg and 96 within 15 mmHg for SBP; and 70 measurements within 5 mmHg, 92 within 10 mmHg and 96 within 15 mmHg for DBP. It passed the criteria for SBP and DBP. For phase 2.2 using the AGILIS monitor, 27 subjects had at least two of the differences within 5 mmHg and none had any differences within 5 mmHg for SBP; 27 subjects had at least two of the differences within 5 mmHg and three subjects had no differences within 5 mmHg for DBP. The results are in concordance with the requested criteria for phase 2.2. CONCLUSION: Thus the AGILIS device fulfils the validation criteria of the international protocol.