Left-sided Heart Disease Research Articles

Retrospective Study to Compare Ring Annuloplasty and Suture Annuloplasty in Tricuspid Valve Diseases

The Tricuspid regurgitation may be primary or secondary to left sided heart disease Residual tricuspid regurgitation is seen after tricuspid valve annuloplasty(TVA) - both ring and suture anuloplasty. A study was conducted in KEM Hospital as to validate the benefits of ring annuloplasty over suture anoloplasty. 80 patients undergoing MVR and TVA were studied. Of these 50 patients underwent MVR with ring annuloplasty and 30 underwent MVR with DeVegas annuloplasty. 2DECHO was done pre and postoperatively to determine pulmonary artery systolic pressure(PASP), grade of tricuspid regurgitation (TR), LV ejection fraction(LVEF) and tricuspid annulus. 82% of patients of ring annuloplasty group had reduction in PASP postoperatively compared to 56% in DeVegas annuloplasty . Grade of TR improved from moderately severe TR to mild TR in 86% in the ring annuloplasty group compared to53% in DeVegas annuloplasty group. 58% of patients of ring annuloplasty had maintained LV function postoperatively compared to 46% of patients in DeVegas annuloplasty.The mean tricuspid annulus showed reduction from preoperative annulus size of 37.72 to 27.5 in ring annuloplasty group and from 37.9to 27.13 in DeVegas annuloplasty group. Tricuspid ring annuloplasty is a better and durable repaire compared to suture annuloplasty for secondary TR. Aggressive management of secondary TR such as this could hopefully decreas the occurence of late TR following previous left sided valve surgery

Shape of the Pulmonary Artery Doppler-Flow Profile Predicts the Hemodynamics of Pulmonary Hypertension Caused by Left-Sided Heart Disease.

Previous studies demonstrated a relationship between pulmonary hemodynamics and shape of pulmonary artery (PA) Doppler-flow profiles in a mixed pulmonary hypertension (PH) cohort. Shape of PA Doppler-flow profiles could illustrate the hemodynamic characteristics of pulmonary venous hypertension (PVH), especially identifying it with or without pulmonary vascular disease (PVD). We retrospectively analyzed hemodynamic, echocardiographic, and clinical data from 47 patients referred for PH caused by left-sided heart disease (PH-LHD). All patients underwent right-sided heart catheterization within 1 week of echocardiography. We concluded a simple echocardiographic prediction rule to give hemodynamic differentiation of PVH with PVD, defined as capillary wedge pressure >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The PA Doppler-flow profiles were categorized into 2 groups, no notch (NN) and MSN/LSN. The PVR was higher in the MSN/LSN group at 4.04 WU (interquartile range, 3.1-5.3) vs the NN group at 1.91 WU (interquartile range, 1.8-3.0; P < 0.001). Pulmonary artery Doppler-flow notching (MSN and LSN) was highly associated with PVR >3 WU, whereas the NN pattern predicted a PVR ≤3 WU (odds ratio: 19.8, 95% confidence interval: 4.3-91.3) and normal transpulmonary pressure gradient ≤12 mm Hg (odds ratio: 4.7, 95% confidence interval: 1.3-16.2). The NN pattern had 74% specificity and 88% sensitivity for PVR ≤3 WU. Absence of PA Doppler-flow notching was highly associated with PVH, and a notching pattern indicated PVH with PVD in the PH-LHD cohort.

40-Year-Old Woman With Breathlessness and Fatigue

40-Year-Old Woman With Breathlessness and Fatigue

Aortic and/or mitral valve surgery in patients with pulmonary hypertension performed via a minimally invasive approach.

Pulmonary hypertension (PH) in the setting of left-sided valvular heart disease is common, and significantly increases the risk of perioperative morbidity and mortality in patients undergoing aortic and/or mitral valve surgery. Minimally invasive valve surgery is associated with a decreased incidence of perioperative complications, and a faster recovery, when compared with conventional sternotomy. In the present study, the outcomes of 569 patients with PH who underwent minimally invasive aortic and/or mitral valve surgery were analysed. The operative mortality was 3.5%, and postoperative strokes occurred in 1.4%. The mean intensive care unit and hospital length of stays were 50 ± 14 h and 7 ± 1 days, respectively. Patients with severe PH (mean pulmonary artery pressure ≥40 mmHg) had a longer duration of postoperative ventilation and intensive care unit length of stay, when compared with mild/moderate PH, and similar clinical outcomes. In conclusion, a minimally invasive approach to aortic and/or mitral valve surgery in patients with PH is safe and feasible, and may be considered as an alternative to conventional median sternotomy.

Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy.

BackgroundRecently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left‐sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM.MethodsNinety subjects with DCM underwent cardiac catheterization and CPX at our hospital. Receiver operator characteristic (ROC) analysis was performed to assess the ability of CPX variables to distinguish between the presence and absence of PH.ResultsOverall mean values were: mean PAP (mPAP), 18.0 ± 9.6 mmHg; plasma brain natriuretic peptide, 233 ± 295 pg/mL; and left ventricular ejection fraction, 30.2 ± 11.0%. Patients were allocated to one of two groups on the basis of mean PAP, namely DCM without PH [mean PAP (mPAP) <25 mmHg; n = 75] and DCM with PH (mPAP ≥25 mmHg; n = 15). A cutoff achieved percentage of predicted peak VO2 (%PPeak VO2) of 52.5% was the best predictor of an mPAP ≥25 mmHg in the ROC analysis (area under curve: 0.911). In the multivariate analysis, %PPeak VO2 was the only significant independent predictor of PH (Wald 6.52, odds ratio 0.892, 95% CI 0.818–0.974; P = 0.011).Conclusions%PPeak VO2 was strongly associated with the presence of PH in patients with DCM. Taken together, these findings indicate that CPX variables could be important for diagnosing PH in patients with DCM.

Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families.

We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. NOTCH1 was screened for mutations in 428 nonsyndromic probands with LS-CHD, and family histories were obtained for all. When a mutation was detected, relatives were also tested. In 148/428 patients (35%), LS-CHD was familial. Fourteen mutations (3%; 5 RNA splicing mutations, 8 truncating mutations, 1 whole-gene deletion) were detected, 11 in familial disease (11/148 (7%)) and 3 in sporadic disease (3/280 (1%)). Forty-nine additional mutation carriers were identified among the 14 families, of whom 12 (25%) were asymptomatic. Most of these mutation carriers had LS-CHD, but 9 (18%) had right-sided congenital heart disease (RS-CHD) or conotruncal heart disease (CTD). Thoracic aortic aneurysms (TAAs) occurred in 6 mutation carriers (probands included 6/63 (10%)). Pathogenic mutations in NOTCH1 were identified in 7% of familial LS-CHD and in 1% of sporadic LS-CHD. The penetrance is high; a cardiovascular malformation was found in 75% of NOTCH1 mutation carriers. The phenotypic spectrum includes LS-CHD, RS-CHD, CTD, and TAA. Testing NOTCH1 for an early diagnosis in LS-CHD/RS-CHD/CTD/TAA is warranted.Genet Med 18 9, 914-923.

Echocardiographic Assessment of Right Ventricular Function by Two-Dimensional Strain In Patients with Left-Sided Valvular Heart Disease: Comparison with Three-Dimensional Echocardiography

Abstract Background: Right ventricular (RV) dysfunction is a well-known predictor of mortality in patients with valvular heart disease (VHD). The assessment of RV function is often difficult due to complex geometry and hemodynamic factors. We aim to analyze RV function in patients with severe mitral and/or aortic valve disease using two-dimensional strain (2DS) imaging and conventional echocardiographic parameters, comparing it with right ventricular ejection fraction (RVEF) measured by three-dimensional echocardiography (3DE). Methods: Fifty-three patients with severe mitral and/or aortic VHD underwent complete transthoracic echocardiogram in the preoperative setting for cardiac surgery, including conventional echocardiographic parameters of RV function and speckle-tracking derived 2DS indices: RV global longitudinal strain (RVGS) and RV free wall longitudinal strain (RVFWS). Conventional echocardiographic and 2DS parameters were compared with real-time 3DE RVEF using Spearman correlation test. For comparison between two groups of patients based on the presence of RV dysfunction (normal RVEF ≥ 44% - A, abnormal RVEF < 44% - B), we used nonparametric Mann-Whitney U test. ROC (receiver operating characteristic) curve analysis was used to assess the clinical utility of all RV function variables in defining RV dysfunction. P values <0,05 were considered statistically significant. Results: We found a significant correlation between all parameters and RVEF (p<0.05), with best results for RV fractional area change (FAC), RVGS, and RVFWS. Dividing the population into two-groups based on RVEF, we found 14 patients with RV dysfunction (27.4%), and significant differences between the groups for all RV function variables. For detection of RV dysfunction defined by 3DE, ROC curve analysis showed the best area under the curve (AUC) for RVGS (0.872), RVFWS (0.851) and FAC (0.932). Conclusions: We observed significant correlation between RVGS, RVFWS and RVEF, with good accuracy in detecting RV dysfunction, comparable to FAC and better than other conventional parameters of RV function assessment. The evaluation of RV myocardial deformation with 2DS may have additional diagnostic and prognostic value in patients with severe left-sided VHD. (Int J Cardiovasc Sci. 2018; [online].ahead print, PP.0-0).

Pulmonary Impedance and Pulmonary Doppler Trace in the Perioperative Period.

Pulmonary hypertension and associated vascular changes may frequently accompany left-sided heart disease in the adult cardiac surgical population. Perioperative assessment of right ventricular function using echocardiography is well established. In general, understanding the constraints upon which the right ventricle must work is mostly limited to invasive monitoring consisting of pulmonary artery pressures, cardiac output, and pulmonary vascular resistance. The latter 2 measurements assume constant (mean) flows and pressures. The systolic and diastolic pressures offer a limited understanding of the pulsatile constraints, which may become significant in disease. In normal physiology, pressure and flow waves display near-similar contours. When left atrial pressure and pulmonary vascular resistance are increased, changes in pulmonary arterial compliance will result in elevated impedance to right ventricular ejection. Pressure reflections, the result of strong reflectors, return more quickly in a noncompliant system. They augment pulmonary artery pressure causing a premature reduction in flow. As a result, pressure and flow waves will now be dissimilar. The impact of vascular changes on right ventricular ejection can be assessed using pulmonary artery Doppler spectral imaging. The normal flow velocity profile is rounded at its peak. Earlier peaks and premature reductions in flow will make it appear more triangular. In some cases, the flow pattern may appear notched. The measurement of acceleration time, the time from onset to peak flow velocity is an indicator of constraint to ejection; shortened times have been associated with increased pulmonary vascular resistance and pressure. Understanding the changes in the pulmonary arterial system in disease and the physics of the hemodynamic alterations are essential in interpreting pulmonary artery Doppler data. Analyzing pulmonary artery Doppler flow signals may assist in the evaluation of right ventricular function in patients with pulmonary vascular disease.

Current Concepts in Management of Pulmonary Hypertension: Fighting the Old Demon with Modern Weapons.

Pulmonary hypertension in children is a rare disease associated with high morbidity and mortality. The pathogenesis is not fully understood. Diagnostic evaluation focuses on ruling out other etiologies of pulmonary hypertension and prognosticating the disease. Congenital heart disease and left sided heart disease associated pulmonary hypertension are more common in children. Therapies for idiopathic pulmonary hypertension have evolved over the past decade. Phosphodiesterase 5 inhibitors (sildenafil, tadalafil), endothelin antagonists (Bosentan and ambrisentan) and prostanoids are the classes of drugs shown to be useful in pulmonary hypertension. However, use of these drugs in children is based on extrapolation of adult usage and on expert consensus rather than based on randomized controlled trial evidence. Despite these advances, the outcomes of various forms of pulmonary hypertension remain poor, especially in India, where some forms of therapy are not available and children often are diagnosed at an advanced stage of disease.

Left ventricular vs. biventricular mechanical support: Decision making and strategies for avoidance of right heart failure after left ventricular assist device implantation

Left ventricular assist devices (LVADs) are safer and provide better survival and better quality of life than biventricular assist devices (BVADs) but end-stage heart failure often involves both ventricles, even if its initial cause was left-sided heart disease. Right ventricular failure (RVF) is also a severe complication in about 25% of patients receiving an LVAD, with high perioperative morbidity (renal, hepatic or multi-organ failure) and mortality. Patients who receive an RV assist device (RVAD) only days after LVAD insertion fare much worse than those who receive an RVAD simultaneously with LVAD implantation. Temporary RVAD support in LVAD recipients with high risk for postoperative RVF can avoid permanent BVAD support. Thus, patients who definitely need a BVAD should already be identified preoperatively or at least intra-operatively. However, although the initial biochemical, hemodynamic and echocardiographic patient profiles at admission may suggest the need for a BVAD, many risk factors may be favorably modified by various strategies that may result in avoidance of RVF after LVAD implantation.This article summarizes the knowledge of risk factors for irreversible RVF after LVAD implantation and strategies to optimize RV function (preoperatively, intra-operatively and post-operatively) aimed to reduce the number of BVAD implantations. Special attention is focused on assessment of RV size, geometry and function in relation to loading conditions with the goal of predicting preoperatively the RV changes which might be induced by RV afterload reduction with the LVAD. The review also provides a theoretical and practical basis for clinicians intending to be engaged in this field.

Dyspnea in left-sided heart disease

Shortness of breath (dyspnea) is a common symptom in left-sided heart disease but clinically, patient symptoms show a high variability. Echocardiography is the mainstay for evaluating whether left-sided heart disease is the cause of dyspnea. If left-sided heart failure is diagnosed, this symptom complex must then be subjected to further etiological evaluation. Hypertensive, ischemic and valvular heart diseases are common, as well as atrial fibrillation. If the patient does not have angina pectoris, testing for ischemic heart disease should be done non-invasively by coronary computed tomography or testing for regional myocardial ischemia. Coronary revascularization is indicated only when a prognostically relevant ischemia of more than 10 % of the left ventricle is diagnosed. Diuretics are important for the relief of dyspnea but do not improve the prognosis of patients. In patients with reduced left ventricular function, combination therapy with angiotensin-converting enzyme (ACE) inhibitors, beta blockers and aldosterone antagonists improve the symptoms and prognosis. For treatment of heart failure with preserved ejection fraction evidence-based measures are still lacking. In this case the recommended therapy consists of optimal treatment of comorbidities, regulation of heart rate and blood pressure and participation in structured exercise programs. Angiotensin receptor blockers and aldosterone antagonists can be given in patients with more severe symptoms even though the available data are very sparse.

Prognostic value of CHA2DS2-VASc score in patients with ‘non-valvular atrial fibrillation’ and valvular heart disease: the Loire Valley Atrial Fibrillation Project

The CHA2DS2VASc score is a clinical risk stratification tool which estimates the risk of stroke and thromboembolism in non-valvular atrial fibrillation (AF). We aimed to establish the value of this score for risk evaluation in patients with non-valvular AF and valvular heart disease. Among 8053 patients with non-valvular AF (ESC guidelines definition), patients were categorized into Group 1 (no valve disease, n = 6851; 85%) and Group 2 (valve disease with neither rheumatic mitral stenosis nor valve prothesis, n = 1202; 15%). After follow-up of 868 ± 1043 days, 627 stroke/ thromboembolic (TE) events were recorded. Group 2 was significantly older, had a higher CHA2DS2VASc score and had a higher risk of thromboembolic events [hazard ratio (HR) 1.39; 95% CI 1.14-1.69, P = 0.001] compared with Group 1. Severe valve disease was not associated with worse prognosis for stroke/TE events. In the two groups, stroke/TE risk increased with a higher CHA2DS2VASc score. Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95% CI 1.14-1.36 per 10-year increase, P < 0.0001) and higher CHA2DS2VASc score (HR 1.33, 95% CI 1.23-1.45, P < 0.0001). The predictive value (c-statistic) of the CHA2DS2VASc score was similar in the two groups. In patients with non-valvular AF, left-sided valvular heart disease (excluding mitral stenosis and protheses) was associated with an increased risk of stroke/TE events. A higher CHA2DS2VASc score in these patients is likely to explain these results.

Noninvasive identification of left-sided heart failure in a population suspected of pulmonary arterial hypertension.

Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R(2)=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases.

Systolic and Mean Pulmonary Artery Pressures: Are They Interchangeable in Patients With Pulmonary Hypertension?

Pulmonary hypertension (PH) is a common complication of numerous diseases, including left-sided heart diseases and chronic lung diseases and/or hypoxia, where PH is associated with exercise limitation and a worse prognosis. Other forms of PH include pulmonary arterial hypertension (PAH), chronic thromboembolic PH (CTEPH), and PH with unclear multifactorial mechanisms. Over the past decade, it has been documented that systolic pulmonary artery pressure (sPAP) may help estimate mean pulmonary artery pressure (mPAP) in adults with high accuracy and reasonably good precision (mPAP = 0.61 sPAP + 2 mm Hg). This strong linear relationship between sPAP and mPAP was unexpected from a classic physiologic point of view. Consistent results have been obtained from independent teams using either high-fidelity micromanometer-tipped PA catheters or fluid-filled catheters. Overall, the strong link between sPAP and mPAP has been documented over a wide range of PAPs, heart rate, cardiac output, wedge pressure, and causes of PH, during changes in posture and activity, and irrespective of patient's sex, age, and BMI. A review of available invasive data confirms that patients with CTEPH and idiopathic PAH matched for their mPAP exhibit essentially similar sPAP. Pressure redundancy may be explained by the dependence of PA compliance upon mPAP. The 25 mm Hg threshold used to define PH accurately corresponds to an sPAP of 38 mm Hg. Although the limits of the echocardiographic estimation of sPAP are widely documented, results from invasive studies may furnish an evidence-based sPAP-derived mPAP value, potentially useful in the multiparameter echocardiographic approach currently used to diagnose and follow patients with PH.

Dramatic improvement of clinical and hemodynamic parameters of a heart transplant candidate with sildenafil treatment

Pulmonary hypertension (PHT) is classically defined as an increase in mean pulmonary arterial pressure ≥25 mm Hg at rest as assessed by right heart catheterization (1). It is associated with various clinical conditions. These clinical conditions are classified into five groups. The treatment modalities for group 1 pulmonary hypertension (pulmonary arterialhypertension (PAH)) have diversified enormously in the last de- cade, including prostanoids, endothelin receptor antagonists, and phos- phodiesterase type-5 inhibitors. Unfortunately, therapeutic options for group 2 patients (pulmonary hypertension associated with left-sided heart disease) haven't evolved much and the prognosis for this group still remains poor. However, sildenafil has been recently shown to have some acute beneficial effects in patients with left heart failure (HF) in some trials (2). In this case presentation we discuss a gentleman with advanced left heart failure who showed dramatic clinical and he- modynamic improvement with oral sildenafil treatment. A 55-year-old gentleman was admitted to our clinic for heart failure decompensation. His medical history included coronary artery bypass surgery, an Implantable Cardioverter Defibrillator (ICD) implantation for primary prevention six years later, and an upgrading of his ICD to Cardiac Resynchronization Therapy (CRT) with his ablation due to fre- quent inappropriate ICD shocks as a consequence of atrial fibrillation. His ejection fraction (EF) was calculated as 25% on transthoracic echo- cardiographic examination. His peak VO2 value was measured as 12 ml/kg/min via a cardiopulmonary stress test. Due to frequent hospi- talizations for decompensation and class 4 symptoms refractory to effective medical therapy, the patient was evaluated as a candidate for heart transplantation. A right heart catheterization (RHC) was per- formed to determine the patient's eligibility for transplantation. Pulmo- nary artery pressures and pulmonary vascular resistance were found to be in the ineligible/gray zone (Table 1). Vasoreactivity testing with do- butamine and nasal oxygen was performed to determine the reversibil- ity of the high pulmonary pressures. A partial decrease in pulmonary artery systolic pressure (about 15%) with stable systemic arterial pres- sure was noted. We decided to add oral sildenafil 50 mg (three times a day) to his ongoing treatment, referring to trials showing beneficial pulmonary hemodynamic effects in patients with advanced heart fail- ure. The patient reported dramatic symptomatic improvement and his

Pulmonary artery diastolic pressure gradient as an indicator of severity of illness in patients with pulmonary hypertension related to left-sided heart disease

Pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is most commonly due to passive backward transmission of elevated left-sided heart pressures. A subgroup of these patients develop pulmonary artery remodeling, resulting in systolic and mean pulmonary artery pressures that are 'reactive' or 'out of proportion' to the elevated left-sided heart pressures. These patients have historically been identified by a transpulmonary gradient (TPG) > 12 mmHg. However, since diastolic pulmonary artery pressures are less susceptible to changes in pulmonary blood flow, a diastolic pulmonary gradient (DPG) ⩾ 7 mmHg may be a superior indicator of worse clinical function and prognosis. Based on measurements from a right-heart catheterization (RHC) database (Baylor College of Medicine, Houston, TX, USA), comparisons of several clinical parameters were made among three Group 2 PH patients: normal TPG and DPG (Group 2A), elevated TPG and normal DPG (Group 2B), and elevated TPG and DPG (Group 2C). Among 173 RHCs, 39 were found to have Group 2 PH. Among these 39 cases, 10 (32%), 13 (32%), and 16 (36%) cases were categorized into Groups 2A, 2B, and 2C, respectively. Group 2C patients had significantly worse 6-min walk distance (308 ± 69 m) than Group 2A (425 ± 81 m) and Group 2B (350 ± 103 m) (p = 0.038). There was no significant difference in cardiac output, cardiac index, and right atrial pressure among the three subgroups. Among patients with Group 2 PH, elevated DPG proved to be a more specific indicator of worse functional status than the historically used TPG. International guidelines and protocols for performing RHC for the assessment and diagnosis of PH should include the measurement of DPG.

Recent strategies in treatment of pulmonary arterial hypertension, a review.

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management.

Roelandt's Young Investigator Award session: Thursday 4 December 2014, 15:30-16:30 * Location: Agora

Roelandt's Young Investigator Award session: Thursday 4 December 2014, 15:30-16:30 * Location: Agora

Array comparative genomic hybridisation testing in CHD.

CHD is the leading cause of mortality due to birth defects. Array comparative genomic hybridisation (aCGH) detects submicroscopic copy number changes and may improve identification of the genetic basis of CHD. This is a retrospective analysis of 1252 patients from a regional referral centre who had undergone aCGH. Of the patients, 173 had CHD. A whole-genome custom-designed oligonucleotide array with >44,000 probes was used to detect copy number changes. Of the 1252 patients, 335 (26.76%) had abnormal aCGH results. Of the 173 patients with CHD, 50 (28.9%) had abnormal aCGH results versus 284 (26.3%) of 1079 non-cardiac patients. There were six patients with CHD who had well-described syndromes such as Wolf-Hirschhorn, trisomy 13, DiGeorge, and Williams. Of the patients with CHD, those with left-sided heart disease had the highest proportion (14/31; 45.13%) of abnormal aCGH results, followed by those with conotruncal heart disease (10/29; 34.48%), endocardial cushion defects (13/50; 26%), complex/other heart disease (12/52; 23.08%), and patent ductus arteriosus (1/11; 9.09%). Patients with CHD are at a substantial risk of having microdeletions and microduplications. The incidence of abnormalities on aCGH analysis is higher than identified with karyotype, and identification of copy number changes may help identify the genetic basis of the specific heart defects. However, aCGH may not have a significant diagnostic yield in those with isolated CHD. Further research using larger data sets may help identify candidate genes associated with CHD.

0356: Prognostic value of CHA2DS2-VASc score in patients with atrial fibrillation and valvular heart disease

The CHA2DS2-VASc score estimates the risk of stroke in non-valvular atrial fibrillation (AF). Nonetheless, there are limited data on the risk of stroke/thromboembolic (TE) complications in AF patients with valvular heart disease, other than those with valvular prosthesis or rheumatic mitral valve disease. Methods Among 8962 patients with AF seen between 2000 and 2010, patients were categorised into Group 1 “non valvular AF” (n=6851; 78%), Group 2 “quasi valvular AF” ie. valve disease with neither rheumatic mitral stenosis nor valve prothesis (n=1202; 13%) and Group 3 “valvular AF” (n=909; 9%) using ESC AF guidelines definition. Results In group 2, 61% of the patients had mitral regurgitation (n=917, non severe in 52%, severe in 9%), 24% had aortic regurgitation (n=414, non severe in 22%, severe in 2%) and 32% had aortic stenosis (n=555, non severe in 18%, severe in 14%). In group 3, 88% of the patients with valvular AF had valve prostheses (n=797) and 14% had mitral stenosis (n=124). After follow up of 884±1084 days, 715 stroke/TE events were recorded. Group 2 was significantly older, had a higher CHA2DS2-VASc score and had a higher risk of TE events (relative risk 1.39; 95%CI 1.14–1.69) compared with Group 1. Severe valve disease was not associated with worse prognosis for stroke/TE events (relative risk 1.12, 95%CI 0.78–1.61). In the 3 groups, stroke/TE risk increased with a higher CHA2DS2-VASc score. Factors independently associated with increased risk of stroke/TE events were older age (RR 1.02, 95%CI 1.01–1.03) and higher CHA2DS2-VASc score (RR 1.33, 95%CI 1.23–1.45). The increased risk of stroke/TE events in patients from Group 2 (compared to those from Group 1) did not reach statistical significance in multivariate analysis. Conclusions In patients with AF, left-sided valvular heart disease (excluding mitral stenosis and protheses) was associated with an increased risk of stroke/TE events. A higher CHA2DS2-VASc score was the main driver of these events.