Jean Noel Trochu

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.

Right Ventricular Systolic Function in Organic Mitral Regurgitation Impact of Biventricular Impairment

Background— To assess the prevalence, determinants, and prognosis value of right ventricular (RV) ejection fraction (EF) impairment in organic mitral regurgitation. Methods and Results— Two hundred eight patients (62±12 years, 138 males) with chronic organic mitral regurgitation referred to surgery underwent an echocardiography and biventricular radionuclide angiography with regional function assessment. Mean RV EF was 40.4±10.2%, ranging from 10% to 65%. RV EF was severely impaired (⩽35%) in 63 patients (30%), and biventricular impairment (left ventricular EF<60% and RV EF⩽35%) was found in 34 patients (16%). Pathophysiologic correlates of RV EF were left ventricular septal function (&bgr;=0.42, P<0.0001), left ventricular end-diastolic diameter index (&bgr;=−0.22, P=0.002), and pulmonary artery systolic pressure (&bgr;=−0.14, P=0.047). Mitral effective regurgitant orifice size (n=84) influenced RV EF (&bgr;=−0.28, P=0.012). In 68 patients examined after surgery, RV EF increased strongly (27.5±4.3–37.9±7.3, P<0.0001) in patients with depressed RV EF, whereas it did not change in others (P=0.91). RV EF ⩽35% impaired 10-year cardiovascular survival (71.6±8.4% versus 89.8±3.7%, P=0.037). Biventricular impairment dramatically reduced 10-year cardiovascular survival (51.9±15.3% versus 90.3±3.2%, P<0.0001; hazard ratio, 5.2; P<0.0001) even after adjustment for known predictors (hazard ratio, 4.6; P=0.004). Biventricular impairment reduced also 10-year overall survival (34.8±13.0% versus 72.6±4.5%, P=0.003; hazard ratio, 2.5; P=0.005) even after adjustment for known predictors (P=0.048). Conclusions— In patients with organic mitral regurgitation referred to surgery, RV function impairment is frequent (30%) and depends weakly on pulmonary artery systolic pressure but mainly on left ventricular remodeling and septal function. RV function is a predictor of postoperative cardiovascular survival, whereas biventricular impairment is a powerful predictor of both cardiovascular and overall survival.

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913613.

Increased beta2-adrenoceptors in doxorubicin-induced cardiomyopathy in rat.

Background The toxicity of doxorubicin, leading to an irreversible heart failure, limits its use as chemotherapeutic agent. The beneficial effects of early administration of β-blocker were reported in patients with heart failure due to doxorubicin, suggesting an important role of β-adrenoceptors (β-ARs). This study aimed to identify a putative target (β-AR and/or its effectors) at the early phase of a chronic doxorubicin-induced cardiomyopathy (Dox-CM) in a rat model. Methodology Dox-CM was induced by six doxorubicin injections (cumulative dose: 15 mg.kg−1) and validated by echocardiography and left ventricle (LV) catheterization. The β-AR protein expressions in LV were evaluated by western-blot at days 35 (d35) and 70 (d70) after the first doxorubicin injection. Ex vivo cardiac contractility (dP/dtmax, dP/dtmin) was evaluated on isolated heart in response to specific β-AR stimulations at d35. Results At d35, Dox-CM hearts were characterized by mild LV systolic and diastolic dysfunctions, which were exacerbated at d70. In Dox-CM hearts, β3-AR expression was only decreased at d70 (-37±8%). At d35, β1-AR expression was decreased by 68±6%, but ex vivo β1-AR function was preserved due to, at least in part, an increased adenylyl cyclase response assessed by forskolin. β2-AR expression was increased both at d35 (+58±22%) and d70 (+174±35%), with an increase of ex vivo β2-AR response at d35. Inhibition of Gi protein with pertussis toxin did not affect β2-AR response in Dox-CM hearts, suggesting a decoupling of β2-AR to Gi protein. Conclusion This study highlights the β1/β2-AR imbalance in early Dox-CM and reveals the important role that β2-AR/Gi coupling could play in this pathology. Our results suggest that β2-AR could be an interesting target at early stage of Dox-CM.

Drug-induced aortic valve stenosis: An under recognized entity

BACKGROUND We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.

Mitral regurgitation — Unmet need for improved management strategies

Background The management of mitral regurgitation (MR) is challenging — patients may be asymptomatic, oligosymptomatic, older with comorbidities, or clinically symptomatic and not appropriate for surgery. The current review assesses morbidity, mortality, and risk factors associated with functional and organic MR, with a focus on severe MR. Methods A structured literature review was conducted in MEDLINE, Embase, the Cochrane Library, and via hand-searching of conference proceedings. Prospective randomised controlled trials and observational studies including adult patients with MR reporting on treatment response rates, survival, time-to-treatment failure, quality of life, and adverse events were eligible for inclusion. Results In total, 32 publications met the inclusion criteria (9 in functional, 18 in organic, and 5 in functional/organic). Despite study heterogeneity, an increased risk of mortality and morbidity was observed which increased with MR severity. Risk factors associated with mortality and morbidity included advancing age, presence of atrial fibrillation, increasing effective regurgitant orifice, ejection fraction, left ventricle end systolic diameter, diabetes, and increasing New York Heart Association class. Conclusions The current review represents one of the most comprehensive conducted in the medical/conservative management of MR. An increased risk of mortality and morbidity, which appeared to rise with greater severity, was associated with MR (versus no MR). An unmet need exists in the management of patients with severe symptomatic MR and a high surgical risk as they have a poor prognosis and limited treatment options. Further research into alternative medical strategies and patient management is needed to improve prognoses and reduce mortality and morbidity.

Congenital anomalous origin of a single coronary artery and high-level sporting competition.

Using a single clinical case of a professional soccer player presenting an anomalous origin of the right coronary artery, cardiac screening and surgical treatment are described taking into account the recommendations of cardiac and sports societies.