Najmeddine Echahidi

Mechanisms, prevention, and treatment of atrial fibrillation after cardiac surgery.

Post-operative atrial fibrillation (POAF) is a frequent complication occurring in 30% to 50% of patients after cardiac surgery. It is associated with an increased risk of mortality and morbidity, predisposes patients to a higher risk of stroke, requires additional treatment, and increases the costs of the post-operative care. The aim of this review is to present the current state of knowledge about the risk factors, mechanisms, prevention, and treatment of this complication. In addition to the well known risk factors for the development of POAF such as age, left atrial enlargement, and valvular surgery, new metabolic risk factors related to visceral obesity have been identified. With regard to the prevention of POAF, beta-blocker drugs are effective and safe and can be used in most patients, whereas amiodarone can be added in high-risk patients. Biatrial pacing was shown to be effective; however, its complexity might limit its application. Although there are only few data regarding the usefulness of magnesium, statins, N-3 polyunsaturated fatty acids, and corticosteroids, their addition to beta-blocker drugs might be of benefit for further reducing POAF. Treatment includes the use of an AV nodal blocking agent to achieve the rate control. If AF does not spontaneously convert to sinus rhythm within 24 h, anticoagulation should be initiated and a rhythm control strategy should be attempted. More investigations are warranted to explore mechanisms by which POAF occurs. This new knowledge would undoubtedly translate into a more efficient prevention and treatment of this common post-operative complication that is associated with a major health and economic burden.

Impact of Prosthesis-Patient Mismatch on Long-Term Survival After Aortic Valve Replacement Influence of Age, Obesity, and Left Ventricular Dysfunction

OBJECTIVES This study was designed to evaluate the effect of valve prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and to determine if this effect is modulated by patient age, body mass index (BMI), and pre-operative left ventricular (LV) function. BACKGROUND We recently reported that PPM is an independent predictor of operative mortality after AVR, particularly when associated with LV dysfunction. METHODS The indexed valve effective orifice area (EOA) was estimated in 2,576 patients having survived AVR and was used to define PPM as not clinically significant if it was >0.85 cm(2)/m(2), as moderate if >0.65 and < or =0.85 cm(2)/m(2), and severe if < or =0.65 cm(2)/m(2). RESULTS After adjustment for other risk factors, severe PPM was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort. Severe PPM was also associated with increased overall mortality in patients <70 years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m(2) (HR: 2.1; p = 0.006), but had no impact in older patients or in obese patients. Moderate PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR: 1.21; p = 0.01), but not in patients with preserved LV function. CONCLUSIONS Moderate PPM is associated with increased late mortality in patients with LV dysfunction, but with normal prognosis in those with preserved LV function. Notwithstanding the previously demonstrated deleterious effect of severe PPM on early mortality, this factor appears to increase late mortality only in patients <70 years old and/or with a BMI <30 kg/m(2) or an LV ejection fraction <50%.

Obesity and Metabolic Syndrome Are Independent Risk Factors for Atrial Fibrillation After Coronary Artery Bypass Graft Surgery

Background— Postoperative atrial fibrillation (POAF) is a highly prevalent complication after cardiac surgery with substantial effects on outcomes. Previous studies have reported that obesity is a risk factor for POAF after cardiac surgery. However, it is unknown whether the metabolic syndrome (MS) also increases the risk of postoperative atrial fibrillation. Methods and Results— We retrospectively analyzed the association between obesity and MS and the incidence of new-onset POAF in a total of 5085 patients who underwent isolated coronary artery bypass grafting surgery with no concomitant valvular surgery. Of these patients, 1468 (29%) were obese (body mass index ≥30 kg/m2) and 2320 (46%) had a MS as defined by the NCEP-ATPIII. POAF occurred in 1374 (27%) of the patients. Obesity was associated (P<0.001) with increased incidence of POAF in the whole cohort as well as in patients >50 years old but not in patients ≤50 years old. In these patients, MS was the only metabolic factor to be significantly associated with higher incidence of POAF (12% versus 6%, P=0.01). In >50-year-old patients, mild (30 ≤ body mass index <35 kg/m2) and moderate–severe (body mass index ≥35 kg/m2) obesity were independently associated with a 1.4-fold (95% CI: 1.10 to 1.71; P=0.004) and 2.3-fold (95% CI: 1.71 to 3.13; P<0.0001) increase in the risk of POAF, respectively. In ≤50-year-old patients, MS (relative risk [RR]: 2.36; 95% CI: 1.10 to 5.12; P=0.02) but not obesity was independently associated with POAF. Conclusion— This study demonstrates that obesity is a powerful risk factor for the occurrence of POAF after isolated coronary artery bypass grafting surgery in patients older than 50 years. However, in the younger population, this association is not observed and MS is the only metabolic risk factor to be independently associated with POAF.

Cardiac amyloidosis: Updates in diagnosis and management

Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment.

Outcome and Impact of Surgery in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction A Cardiac Catheterization Study

Background— The clinical relevance and management of paradoxical low-flow, low-gradient aortic stenosis (LFLG-AS) with preserved left ventricular ejection fraction remain debated. The aim of this study is to determine the features and outcome of LFLG-AS assessed using cardiac catheterization. Methods and Results— Between 2000 and 2010, 768 patients with preserved left ventricular ejection fraction (>50%) and severe AS (valve area ⩽1cm2) without other valvular disease underwent cardiac catheterization. Mean age was 74±8 years, 42% were women, and 46% had associated coronary artery disease. The prevalence of LFLG (indexed left ventricular stroke volume <35 mL/m2 and mean gradient <40 mm Hg), normal flow high gradient, normal flow low gradient, and low flow high gradient were 13%, 50%, 22%, and 15%, respectively. Compared with patients with normal flow high gradient, those with LFLG were significantly older, with significantly reduced systemic arterial compliance and vascular resistances and increased valvulo-arterial impedance (all P<0.05). Ten-year survival was reduced in LFLG-AS (32±9%) compared with normal flow high gradient (66±4%; P=0.0002). After adjustment for other risk factors, LFLG-AS was independently associated with reduced long-term survival (hazard ratio, 1.85; 95% confidence interval, 1.08–3.07; P=0.02). However, despite higher operative mortality, patients with LFLG-AS undergoing aortic valve replacement seemed to have better long-term survival than those managed conservatively (5-year survival rate: 63±6% versus 38±15%; P=0.007; hazard ratio, 0.23; 95% confidence interval, 0.09–0.59; P=0.002). Conclusions— This large cardiac catheterization–based study reports that the LFLG-AS entity is not rare and is associated with worse outcome whether treated medically or surgically. However, these patients may have better long-term survival if treated surgically. Further prospective studies are needed to confirm this finding.

Prevalence and Long-Term Outcome of Aortic Prosthesis–Patient Mismatch in Patients With Paradoxical Low-Flow Severe Aortic Stenosis

Background— Patients with severe aortic stenosis (AS) and paradoxical low flow (PLF) have worse outcome compared with those with normal flow. Furthermore, prosthesis–patient mismatch (PPM) after aortic valve replacement is a predictor of reduced survival. However, the prevalence and prognostic impact of PPM in patients with PLF-AS are unknown. We aimed to analyze the prevalence and long-term survival of PPM in patients with PLF-AS. Methods and Results— Between 2000 and 2010, 677 patients with severe AS, preserved left ventricular ejection fraction, and aortic valve replacement were included (74±8 years; 42% women; aortic valve area, 0.69±0.16 cm2). A PLF (indexed stroke volume ⩽35 mL/m2) was found in 26%, and after aortic valve replacement, 54% of patients had PPM, defined as an indexed effective orifice area ⩽0.85 cm2/m2. The combined presence of PLF and PPM was found in 15%. Compared with patients with noPLF/noPPM, those with PLF/PPM were significantly older, with more comorbidities. They also received smaller and biological bioprosthesis more often (all P<0.01). Although early mortality was not significantly different between groups, the 10-year survival rate was significantly reduced in case of PLF/PPM compared with noPLF/noPPM (38±9% versus 70±5%; P=0.002), even after multivariable adjustment (hazard ratio, 2.58; 95% confidence interval, 1.5–4.45; P=0.0007). Conclusions— In this large catheterization-based study, the coexistence of PLF-AS before surgery and PPM after surgery is associated with the poorest outcome.

Left atrial size is an independent predictor of overall survival in patients with primary systemic amyloidosis.

BACKGROUND Primary systemic amyloidosis is a severe plasma cell disorder characterized by the extracellular deposition of amyloid fibrils in different organs. Echocardiography is usually performed to assess cardiac involvement. We hypothesized that in patients with systemic amyloidosis, simple echocardiographic measurement of the left atrial (LA) diameter indexed to the body surface area might provide an important risk marker for this disease. METHODS Between 1997 and 2011, 134 patients were diagnosed with primary systemic amyloidosis and had echocardiography within 28 days; we collected their baseline characteristics and biological and echocardiographic data retrospectively. LA enlargement was defined as recommended as M-mode LA diameter greater or equal to 23 mm/m(2). RESULTS One hundred and eleven patients (83%) had echocardiographic LA dimension data available (mean age 63±11 years; 61% men; 31% previously diagnosed with systemic hypertension). Mean left ventricular ejection fraction (LVEF) and interventricular septum thickness (IVST) were 62±12% and 14±4 mm, respectively. Mean follow-up was 2.8±2.9 years (maximum 12 years). Patients with LA enlargement had a slightly lower LVEF (P=0.08) and a significantly greater IVST (P<0.0001). Overall, 5-year survival was 57±5%. However, 1-year and 5-year survival rates were markedly reduced in patients with LA enlargement versus those without LA enlargement (61±7% and 39±8% vs 83±5% and 72±7%, respectively; P=0.0007). On multivariable analysis, after adjusting for age, sex, LVEF, IVST, presence of hypertension and creatinine concentration, LA enlargement remained an independent predictor of overall mortality at 5 years (hazard ratio 2.47; 95% confidence interval 1.11-5.90; P=0.02). CONCLUSION LA enlargement, a surrogate marker of diastolic dysfunction, is an independent predictor of long-term mortality and may therefore help to enhance risk stratification and management of patients presenting with amyloidosis.

A novel mutation in a large French-Canadian family with LGMD1B.

BACKGROUND Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death. OBJECTIVE Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B. METHODS We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies. RESULTS The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C > G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation. CONCLUSIONS We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.

Reduced systemic arterial compliance measured by routine Doppler echocardiography: A new and independent predictor of mortality in patients with type 2 diabetes mellitus

OBJECTIVES This study was designed to examine the prognostic value of systemic arterial compliance (SAC) by Doppler-echocardiography in patients with type 2 diabetes mellitus (T2D). BACKGROUND Reduced SAC has been shown to predict outcomes in patients with hypertension. T2D is associated with accelerated arterial stiffening and increased cardiovascular events. We hypothesized that SAC measured by Doppler-echocardiography would independently predict mortality in patients with T2D. METHODS Since 2001, SAC calculated as the ratio of stroke volume index to arterial pulse pressure by sphygmomanometer is routinely performed in our laboratory. Data from 505 consecutive patients with T2D were retrospectively analyzed. Based on a previously validated cut-off value of SAC < 0.6 ml/m(2)/mmHg, patients were divided into Group 1, reduced SAC, 255 patients (50%) and Group 2, preserved SAC, 250 patients (50%). The primary endpoint was overall mortality. RESULTS Patients with reduced SAC had significantly lower 5-year survival than those with preserved SAC (66 ± 5 vs. 82 ± 5%, p = 0.02) and a 1.57-fold (95% CI: 1.04-2.43; p = 0.03) increased risk of mortality after adjusting for other risk factors. Blood pressure did not predict mortality and pseudo-normalized blood pressures related to LV dysfunction and low cardiac output were found in 75 patients (15%). CONCLUSION Reduced SAC is encountered frequently in T2D, is an independent predictor of mortality and allows identification of patients who, despite a normal blood pressure, are at increased risk. Future studies are necessary to further evaluate the clinical utility of this simple echocardiographic parameter and therapies are needed to alter vascular stiffness to improve clinical outcomes in these high-risk patients.

Usefulness of Transesophageal Echocardiography in the Isolation of Pulmonary Veins in the Treatment of Atrial Fibrillation

Background: New imaging strategies for atrial fibrillation (AF) ablation should enhance the safety of this technique. The role of transesophageal echocardiography (TEE) in this setting has not been prospectively evaluated.