Dania Mohty

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

No abstract available nKeywords: European Society of Cardiology; arrhythmias; cancer therapy; cardio-oncology; cardiotoxicity; chemotherapy; early detection; ischaemia; myocardial dysfunction; surveillance.

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 mmu2009Hg), 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.

Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III)

Bortezomib is an active agent in AL amyloidosis and responses to this drug in combination with cyclophosphamide and dexamethasone are both rapid and deep. Here we present an international, multicenter series of 60 patients with Mayo Clinic stage III cardiac amyloidosis to assess the impact of this regimen in improving outcomes in this poor-risk group. The median follow-up for the entire cohort is 11.8 months. The overall response rate was 68%. In a landmark analysis, examining patients who survived more than 3 months, the overall response rate was 86%. A cardiac response was seen in 32% of patients. The estimated 1-year survival rate for the whole cohort was 57% and 24 patients (40%) died while on therapy. Although unable to save the poorest risk patients, the combination of bortezomib, cyclophosphamide and dexamethasone can achieve a high number of hematologic and cardiac responses, likely improving overall survival and justifying a prospective trial.

Effectiveness of Screening for Abdominal Aortic Aneurysm During Echocardiography

Screening patients with abdominal aortic aneurysm (AAA) is associated with reduced AAA-related mortality, but population screening is poorly implemented. Opportunistic screening during imaging for other indications might be efficient. Single-center series reported AAA rates of 0.8% to 6.5% in patients undergoing transthoracic echocardiography (TTE), with disparities due to selection bias. In this first multicenter study, we aimed to assess the feasibility and criteria for screening AAA during TTE in real-life practice. During a week of May 2011, 79 centers participated in a nationwide survey. All patients aged ≥65 years requiring TTE for any indication were eligible, except for those with operated abdominal aorta. We defined AAA by an anteroposterior diameter of the infrarenal aorta≥30 mm. Of 1,382 consecutive patients, abdominal aorta imaging was feasible in 96.7%, with a median delay of 1.7 minutes (>3 minutes in 3.6% of cases). We found AAA in 50 patients (3.7%). Unknown AAA (2.7%) was more frequent in men than women (3.7% vs 1.3%, respectively, p=0.007) and increased by age at 2.2%, 2.5%, and 5.8% in age bands of 65 to 74, 75 to 84, and 85+ years, respectively. None of the female participants aged <75 years had AAA. Smoking status and family history of AAA were significantly more frequent among patients with AAA. The ascending aorta was larger in those with AAA (36.2±4.7 vs 34.0±5.2 mm, p=0.006), and bicuspid aortic valve and/or major aortic regurgitation were also more frequent (8% vs 2.6%, p=0.017). In conclusion, rapid AAA screening during TTE is feasible and should be limited to men ≥65 years and women≥75 years.

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Authors/Task Force Members: Jose Luis Zamorano* (Chairperson) (Spain), Patrizio Lancellotti* (Co-Chairperson) (Belgium), Daniel Rodriguez Muñoz (Spain), Victor Aboyans (France), Riccardo Asteggiano (Italy), Maurizio Galderisi (Italy), Gilbert Habib (France), Daniel J. Lenihan (USA), Gregory Y. H. Lip (UK), Alexander R. Lyon (UK), Teresa Lopez Fernandez (Spain), Dania Mohty (France), Massimo F. Piepoli (Italy), Juan Tamargo (Spain), Adam Torbicki (Poland), and Thomas M. Suter (Switzerland)

Prevalence of peripheral artery disease in the elderly population in urban and rural areas of Central Africa: the EPIDEMCA study

Objective Data on peripheral artery disease in Africa are sparse and limited to urban areas. Given the urban/rural socio-economical gradient in these countries, we sought to determine the prevalence and risk factors of peripheral artery disease in urban and rural areas of two countries in Central Africa. Methods Individuals ≥65 years old living in two urban and rural areas of the Republic of Central Africa (ROC) and the Central African Republic (CAR) were invited. Demographic, clinical and biological data were collected. Ankle-brachial index ≤0.90 defined peripheral artery disease. Results Among the 1871 participants (age 73 years, 62% female) the prevalence of peripheral artery disease was 14.8%, higher in ROC than in CAR (17.4% vs. 12.2%, pu2009=u20090.007) and higher in females than males (16.6% vs. 11.9%, pu2009=u20090.012). The prevalence of peripheral artery disease increased with age, respectively at 10.9%, 14.9%, 15.1% and 22.2% for age bands of 65–69, 70–74, 75–79 and 80+years (pu2009<u20090.001). Higher rates of peripheral artery disease were found in urban areas in ROC (20.7% vs. 14.4% in rural areas, pu2009=u20090.011), but not in CAR (11.5% vs. 12.9%, pu2009=u2009NS). In multivariate analysis, peripheral artery disease was significantly associated with age (odds ratio (OR): 1.03; pu2009=u20090.004), dyslipidaemia (OR: 1.88; pu2009=u20090.003), smoking (OR: 1.78; pu2009=u20090.003), obesity (OR: 1.98; pu2009=u20090.034) and underweight (OR: 1.49; pu2009=u20090.023). Regular alcohol drinking was associated with decreased risk of peripheral artery disease (OR: 0.73; pu2009=u20090.044). Conclusion The prevalence of peripheral artery disease in the elderly is high in Africa, especially in females. In ROC, with a higher urban-rural socio-economic gradient, peripheral artery disease is more frequent in the urban areas.

Paradoxical low-flow, low-gradient severe aortic stenosis: a distinct disease entity

Low-flow, low-gradient (LFLG) severe aortic stenosis (AS), despite preserved LVEF, that is, paradoxical LFLG, is one of the most challenging entities in valvular heart disease.1 Hachicha et al were the first to report that patients with small aortic valve area (AVA) and preserved LVEF may concomitantly have an LF and thus often low gradient.1 This new entity is defined as an AVA ≤1.0u2005cm2 or indexed AVA ≤0.6u2005cm2/m2, a mean pressure gradient (MPG) <40u2005mmu2005Hg, an LVEF ≥50% and a stroke volume index (SVi) <35u2005mL/m2. The most recent European2 and American3 guidelines have recognised paradoxical LFLG AS as an important entity that deserves particular attention and recommend surgery as class IIa indication for surgery if the severity and the relationship with symptoms are confirmed. Recent studies however reported some conflicting results with regard to the natural history and outcomes of paradoxical LFLG AS (online supplement) reflecting the patient heterogeneity and the complexity of this entity.nnIt is frequently assumed that normal LVEF implies normal LV systolic function and normal transvalvular flow and, consequently, high transvalvular gradient in the presence of severe AS. However, this common belief has been challenged by several recent studies, which reported that many (20%–50%) patients with AS and normal LVEF, paradoxically, have reduced SVi and thus a low cardiac output and transvalvular flow rate (online supplement). This LF state makes assessment of AS severity more complex because standard resting echocardiography or catheterisation parameters (peak jet velocity, MPG and AVA) may not reflect the true severity of stenosis. Indeed, the gradient, which is highly flow dependent, may be ‘pseudo-normalised’ and thus underestimate the severity of the stenosis.nnInitially, this paradox was explained by the concept that patients with severe AS often have pronounced concentric LV remodelling with impaired …

Renal Artery Stenosis in Patients with Peripheral Artery Disease: Prevalence, Risk Factors and Long-term Prognosis

OBJECTIVE/BACKGROUNDnThe objective was to determine the prevalence and clinical determinants of renal artery stenosis (RAS) in patients undergoing digital subtraction angiography (DSA) for the assessment of peripheral artery disease (PAD), and to evaluate its prognostic significance.nnnMETHODSnAll DSAs performed from January 2000 to January 2006 were retrospectively reviewed for assessment of PAD in patients naive for any prior revascularisation of lower-limb arteries. All DSA studies were read by two senior physicians blinded to outcome, and consensus was reached in cases of disagreement. RAS was defined as the presence of ≥50% stenosis in either renal artery. Patients electronic medical files were systematically reviewed and follow-up was completed by contact with family physicians until January 2014. The primary outcome was composite, including death, peripheral revascularisation, or any limb amputation. Secondary outcomes were all-cause mortality, and another composite, including death and non-fatal myocardial infarction or stroke or coronary or carotid revascularisation.nnnRESULTSnIn total, 400 consecutive patients having a first DSA of lower extremities, two thirds of whom were for critical limb ischaemia, were studied. Thirteen patients were excluded owing to poor renal artery imaging. RAS was detected in 57 patients (14%). Only two factors were independently and significantly associated with RAS in multivariate analysis: diffuse PAD (involving both proximal and distal segments [odds ratio {OR} 3.50, 95% confidence interval {CI} 1.16-10.54; pxa0=xa0.026]) and decreased glomerular filtration rate (OR 0.55 per 30 mL/minute/1.73xa0m2, 95% CI 0.41-0.75; pxa0<xa0.001). During follow-up (meanxa0±xa0SD 62xa0±xa047 months), 25% experienced limb amputation and 54% died. In multivariate analysis, no significant association was found between RAS and primary outcome (hazard ratio 0.80; 95% CI 0.57-1.10). No significant association was found with secondary outcomes.nnnCONCLUSIONnIncidental RAS is frequent (14%) among patients with PAD undergoing lower extremity imaging. No difference in outcome in patients with RAS versus those without RAS was seen. Larger studies are necessary to draw definite conclusions.

Prognosis importance of low flow in aortic stenosis with preserved LVEF

Aims Previous studies using echocardiography suggested that a low flow (LF) defined as an indexed stroke volume (SVi) <35u2005mL/m2 may be an important determinant of outcome in patients with severe aortic stenosis (AS). We sought to assess the prognostic importance of stroke volume derived from invasive data. The aim of this study was to determine the impact of LF, purposely derived from cardiac catheterisation data, on outcome of patients with severe AS and preserved LVEF. Methods Between 2000 and 2010, 768 patients with preserved LVEF (>50%) and severe AS (valve area ≤1u2005cm2) without other valvular heart disease underwent cardiac catheterisation. The long-term overall mortality was assessed as the primary end-point. Results Mean age was 74±8u2005years, 58% were men, 46% had coronary artery disease and mean LVEF was 72±10%. Low SVi was found in 27% (n=210) of patients with AS. As compared with patients with normal SVi, those with low SVi were significantly older (p<0.0001) with higher rate of atrial fibrillation (p<0.0001). Additionally, they had lower LVEF (p=0.046), aortic valve area (p<0.0001), mean pressure gradient (p<0.0001), systemic arterial compliance (p<0.0001) and higher systemic vascular resistances (p<0.0001). Eight-year survival was significantly reduced in patients with low SVi as compared with those with normal SVi (51±5% vs 67±3%; p<0.0001). After adjustment for all other risk factors, reduced SVi was independently associated with long-term mortality (HR=1.45, 95% CI 1.1 to 2.1; p=0.048). Conclusions In patients with severe AS and preserved LVEF, LF, as assessed using cardiac catheterisation is frequent, and is an independent predictor of mortality. Consequently, the measurement of SVi should be systematically included in the assessment of these patients.

Prevalence and prognostic impact of left-sided valve thickening in systemic light-chain amyloidosis

BackgroundLeft heart valve thickening (LVT) was described in patients with light-chain amyloidosis (AL). This phenomenon reflects likely infiltration of the valve by amyloid proteins. However, the prevalence of LVT and its prognostic value have not been investigated in patients with AL.Methods and resultsComprehensive transthoracic echocardiography was performed at baseline in 150 patients [median age 68 (33–87) years; 59% male] with confirmed AL. The presence of abnormal mitral and/or aortic valve thickening (>3xa0mm) was assessed in all included patients. Overall, 42% had LVT at the time of diagnosis. Compared to patients without LVT, those with LVT were older and had a more advanced NYHA functional class (63% in patients with NYHA III-IV vs. 33% in NYHA I–II, pxa0<xa00.001). They also had higher left ventricular (LV) wall thickness and mass, larger left atrium, higher mitral annulus E/E’ ratio and systolic pulmonary artery pressures, and lower LV ejection fraction (all pxa0<xa00.05). Patients with more advanced Mayo Clinic stage had a higher incidence of LVT: 58% in stage III vs. 45% in stage II and 5% in stage I (pxa0<xa00.001). During a median follow-up of 2xa0years, 79 deaths occurred. The presence of LVT was significantly associated with reduced 5-year survival (32xa0±xa07 vs. 64xa0±xa06%). In multivariate analysis, after adjusting for age, gender, NYHA functional class, and LV ejection fraction, LVT remained significantly associated with higher all-cause mortality (hazard ratio 1.90, 95% CI 1.10–3.34, pxa0=xa00.02).ConclusionLeft heart valve thickening is common in patients with AL and is associated with worse functional class, LV systolic and diastolic function, and more advanced stage of the disease. In addition, LVT appears to be a powerful marker of all-cause mortality.