Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study.

BACKGROUND: Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. METHOD: Serum IF1 levels were measured in 577 male participants with stable CAD (age 45-74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. RESULTS: IF1 levels were positively correlated with HDL-C (r s = 0.40; P < 0.001) and negatively with triglycerides (r s = -0.21, P < 0.001) and CAD severity documented by the Gensini score (r s = -0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38-0.89 and 0.50 (0.28-0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02). CONCLUSIONS: We investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy.

New concept of myocardial longitudinal strain reserve assessed by a dipyridamole infusion using 2D-strain echocardiography: the impact of diabetes and age, and the prognostic value.

AIMS: Although dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography. METHODS: Seventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard. RESULTS: Mean LSR was -2.28±2.19% and was more important in the 28 (44%) diabetic patients (-3.27±1.93%; p=0.001). After multivariate analyses, only diabetes improved LSR (p=0.011) after dipyridamole infusion and was not associated with glycaemic control (p=0.21), insulin therapy (p=0.46) or duration of the disease (p=0.80). Conversely, age (p=0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p=0.005). Patients with a LSR<0% have a better survival after 15 months (log-rank p=0.0012). CONCLUSION: LSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value.

Absolute iron deficiency without anaemia in patients with chronic systolic heart failure is associated with poorer functional capacity.

BACKGROUND: Functional status is one of the main concerns in the management of heart failure (HF). Recently, the FAIR-HF and CONFIRM-HF trials showed that correcting anaemia using intravenous iron supplementation improved functional variables in patients with absolute or relative iron deficiency. Relative iron deficiency is supposed to be a marker of HF severity, as ferritin concentration increases with advanced stages of HF, but little is known about the impact of absolute iron deficiency (AID). AIMS: To study the impact of AID on functional variables and survival in patients with chronic systolic HF. METHODS: One hundred and thirty-eight non-anaemic patients with chronic systolic HF were included retrospectively. Patients were divided into two groups according to iron status: the AID group, defined by a ferritin concentration<100µg/L and the non-AID group, defined by a ferritin concentration≥100µg/L. Functional, morphological and biological variables were collected, and survival was assessed. RESULTS: Patients in the AID group had a poorer 6-minute walking test (342 vs. 387m; P=0.03) and poorer peak exercise oxygen consumption (13.8 vs. 16.0mL/min/kg; P=0.01). By multivariable analysis, ferritin<100µg/L was associated with impaired capacity of effort, assessed by peak exercise oxygen consumption. By multivariable analysis, there was no difference in total mortality between groups, with a mean follow-up of 5.1±1.1 years. CONCLUSIONS: The poorer functional evaluations in iron-deficient patients previously reported are not caused by the merging of two different populations (i.e. patients with absolute or relative iron deficiency). Our study has confirmed that non-anaemic HF patients with AID have poorer peak oxygen consumption. However, AID has no impact on the survival of these patients.

Obesity Paradox: Origin and best way to assess severity in patients with systolic HF.

OBJECTIVE: Obesity in patients with heart failure (HF) is a factor of better prognosis, supposedly partly because of the particular epidemiology of HF in this population. This study expected to compare the parameters of severity and mortality in patients with and without obesity, to better understand the origin of this paradox. METHODS: Two hundred twenty-two patients with nonischemic HF and systolic dysfunction were divided into two groups according to their body mass index (≥ 30 vs. < 30 kg/m(2), respectively) and explored for functional parameters and prognosis. RESULTS: B-type natriuretic peptide (BNP) levels were lower and peak oxygen consumption higher in patients with obesity. Patients with obesity had a better prognosis than patients without obesity with a 4-year mortality of 11.1% and 26.4%, respectively (P = 0.009). By univariate analysis, obesity was associated with a reduced risk of death: HR 0.52 [0.28-0.99]. This protective effect was no longer present after adjusting for VO2max and BNP level. CONCLUSIONS: The obesity paradox is probably partly due to an overestimation of the severity of HF in patients with obesity because of the multifactorial nature of their dyspnea. Obesity no longer has a protective effect after adjustment for the usual prognostic parameters of HF.

Outcomes of Patients Undergoing Balloon Aortic Valvuloplasty in the TAVI Era: A Multicenter Registry.

BACKGROUND: Few clinical data about indications and prognoses of patients undergoing balloon aortic valvuloplasty (BAV) in the transcatheter aortic valve implantation (TAVI) era have been reported. METHODS: Data from all consecutive patients undergoing BAV in seven European centers from 2006 to 2013 were collected. Acute results and long-term outcomes were assessed. RESULTS: A total of 811 patients aged 82 ± 9 years were included; 416 patients (51%) underwent BAV as palliative destination therapy, 320 patients (40%) as bridge to TAVI, and 75 patients (9%) as bridge to surgical aortic valve replacement (SAVR). Patients undergoing BAV as destination therapy had a higher risk profile (logistic EuroSCORE, 20 ± 17 vs 22 ± 14 vs 11 ± 8, respectively; P<.001). Post procedure, peak gradient decreased from 87 ± 22 mm Hg to 66 ± 22 mm Hg (P<.001) and aortic valve area increased from 0.61 ± 0.2 cm2 to 0.8 ± 0.2 cm2 (P<.001). At 30 days, the all-cause death rate (6.5% vs 6.2% vs 7.4%, respectively; P=.56) and the rate of life-threatening and major bleedings (8.0% vs 5.7% vs 6.0%, respectively) did not differ between groups. After a mean follow-up of 318 days (range, 116-500 days), rates of all-cause death were similar (30% vs 34% vs 31%, respectively; P>.99), although patients undergoing BAV as bridge to SAVR showed a lower cardiovascular death rate (11% vs 11% vs 3%, respectively; P=.04). CONCLUSION: In the TAVI era, BAV may represent a reasonable option for patients with severe aortic stenosis and temporary contraindications to definite therapy. Given the mortality rates at 30 days, patients should be carefully selected, while events at follow-up are deeply influenced by the decision of whether or not subsequent interventions are performed.

Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of Frequent Atrial Premature Beats, a New Cause for Arrhythmia-Induced Cardiomyopathy.

Incessant atrial premature beats as a potential cause for tachycardia-induced cardiomyopathy was suspected in a patient presenting with dilated non-ischemic cardiomyopathy and severely altered left ventricular ejection fraction. The elimination of a left atrial focus by percutaneous RF ablation led to normalization of the clinical status, of atrial and ventricular dimensions and left ventricular systolic function.

The major element of 1-year prognosis in acute coronary syndromes is severity of initial clinical presentation: Results from the French MONICA registries.

BACKGROUND: While the death rate from acute coronary syndromes (ACS) has been in decline for more than 50 years, out-of-hospital mortality remains high despite improvements in care. AIM: To evaluate the importance of out-of-hospital mortality and identify the main predictors of in-hospital and 1-year mortality in France. METHODS: Analyses were based on data from the French MONICA population-based registry, which included all cases of ACS occurring in people aged 35-74 years during 2006 in three geographic areas in France. We first evaluated out-of-hospital mortality; then, using data from patients with incident ACS who reached hospital alive, Cox models were performed to determine the main predictors of 1-year mortality. The number of attributable deaths was assessed for variables of interest. RESULTS: After 1-year follow-up, case-fatality was 29.3% for incident events (n=2547); the proportion of out-of-hospital deaths was 70.3%, and 91.5% of deaths occurred in the 28 days following the ACS. On multivariable analysis, the number of attributable deaths associated with three scenarios (out-of-hospital life-and-death emergency, hospitalization before ACS occurrence, and lack of coronary angiography) was 130 (accounting for 59% of deaths occurring after reaching the hospital) during 1-year follow-up. These scenarios corresponded to patients with an initial severe clinical presentation in whom rates of use of specific treatments and invasive procedures were very low. CONCLUSION: A large proportion of fatalities after an ACS occurs in the out-of-hospital phase. Moreover, the major component of 1-year mortality is associated with a poor prognosis at initial presentation. This finding highlights the importance of cardiovascular prevention, population education and better out-of-hospital emergency management in improving prognosis after an ACS.