Vasopressin in Patients with Septic Shock and Dynamic Left Ventricular Outflow Tract Obstruction.

PURPOSE: Left ventricular outflow tract obstruction (LVOTO) is a relatively uncommon but severe condition that may lead to hemodynamic impairment. It can be elicited by morphological (left ventricular hypertrophy, sigmoid septum, prominent papillary muscle, prolonged anterior mitral valve leaflet) and functional (hypovolemia, low afterload, hypercontractility, catecholamines) factors. We sought to determine the incidence of the most severe form of LVOTO in septic shock patients and describe the therapeutic effects of vasopressin. METHODS: Over a period of 29 months, 527 patients in septic shock were screened for LVOTO. All were mechanically ventilated and treated according to sepsis bundles, including pre-load optimization and norepinephrine infusion. Vasopressin was added in addition to norepinephrine to reduce the adrenergic burden and decrease LVOTO. RESULTS: Ten patients were diagnosed with the most severe form of LVOTO, including systolic anterior mitral valve motion (SAM) and severe mitral regurgitation (MR) with pulmonary oedema. The median norepinephrine dosage to obtain a mean arterial pressure of ≥70 mmHg was 0.58 mcg/Kg/min (IQR 0.40-0.78). All patients had a hyper-contractile left ventricle, septal hypertrophy, significant LVOTO (peak gradient 78 [56-123] mmHg) associated with SAM and severe MR with pulmonary oedema. Vasopressin (median 4 IU/h) allowed a significant reduction of norepinephrine (0.18 [0.14-0.30] mcg/kg/min; p = 0.01), LVOT gradient (35 [24-60] mmHg; p = 0.01) and MR with a significant paO2/FiO2 increase (174 [125-213] mmHg; p = 0.01). CONCLUSION: Vasopressin allowed a reduction of norepinephrine with subsequent LVOTO reduction and hemodynamic improvement of the most severe form of LVOTO, which represented 1.9% of all septic shock patients.

Incidence and Risk Factors for Right Ventricular Outflow Tract Obstruction after the Arterial Switch Operation.

BACKGROUND: The aim of this study was to evaluate the incidence and risk factors for the development of right ventricular outflow tract obstruction (RVOTO) after the arterial switch operation (ASO). METHODS: Between 1983 and 2014, a total of 688 patients underwent ASO. RVOTO was defined as any obstruction of the right ventricular outflow tract (RVOT) requiring reintervention. RESULTS: RVOTO developed in 79 patients (11%) at a median time of 3.8 years (range, 1 day-23.6 years) after ASO. Freedom from RVOT reintervention was 96 ± 1, 89 ± 1, and 83 ± 2% at 1, 10, and 25 years, respectively. Independent risk factors for the development of RVOTO in a Cox's regression model were side-by-side great arteries (p < 0.001), aortic arch anomalies (p < 0.001), use of a pericardial patch for augmentation of the coronary buttons (p < 0.001), and a peak gradient more than 20 mm Hg over the RVOT at discharge (p < 0.001). CONCLUSION: The incidence of RVOTO after ASO is not negligible. Complex morphology, such as side-by-side great arteries and aortic arch anomalies influences the development of RVOTO.

Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.

BACKGROUND: Brugada syndrome (BrS) is an autosomal dominant disease responsible for sudden cardiac death in young individuals without structural anomalies. The most critical part in the management of this channelopathy is identification of high-risk patients, especially asymptomatic subjects. Prior studies have shown that conduction delay in the right ventricular outflow tract (RVOT) is the main mechanism for developing ventricular tachyarrhythmia (VTA) in BrS patients. The aim of this study was to investigate the significance of electrocardiographic RVOT conduction delay parameters as predictors for development of VTA in patients with BrS. METHODS AND RESULTS: We retrospectively analyzed electrocardiograms obtained from 147 BrS patients (43 ± 15 years, 65% men) and assessed the following electrocardiographic parameters: (1) Tzou criteria (V1R > 0.15 mV, V6S > 0.15 mV, and V6S:R > 0.2), (2) prominent S wave in lead I, lead II, and lead III, (3) SII > SIII, and (4) prominent Q wave in lead III as possible predictors of VTA occurrences during follow-up. Prominent SI, SII, SIII, SII > SIII, QIII, and +ve Tzou criteria occurred more frequently in patients who either presented with VTA or developed VTA during the follow-up of 56 (IQR: 40-76) months. SII > SIII has the highest area under the curve for prediction of VTA (AUC: 0.84, sensitivity: 80%, specificity: 89%). Multivariable regression analysis showed that prominent S waves in lead I, SII > SIII and +ve Tzou criteria are independent predictors for VTA in BrS patients. CONCLUSION: Prominent S in lead I, SII > SIII and +ve Tzou criteria can be used as effective signs for predicting VTA in patients with BrS.

Incidence, predictors, and midterm clinical outcomes of left ventricular obstruction after transcatheter aortic valve implantation.

OBJECTIVES: We aimed to evaluate the incidence and midterm clinical outcomes of left ventricular obstruction (LVO) after transcatheter aortic valve implantation (TAVI). BACKGROUNDS: LVO is occasionally unmasked following valve replacement for severe aortic stenosis. However, little is known about the prevalence and effects of LVO after TAVI. METHODS: A total of 158 patients who underwent TAVI in our center between October 2013 and November 2015 received echocardiographic evaluations at baseline; before hospital discharge; and at 3, 6, and 12 months after TAVI. LVO was defined as a peak pressure gradient >30 mm Hg. RESULTS: Over 1 year of follow-up after TAVI, 21 patients (13.3%) demonstrated postprocedural LVO. The incidence was highest at 3-months follow-up and decreased at 6 months or later. Of the 21 patients with LVO, 20 (95.2%) demonstrated midventricular obstruction (MVO), whereas only 1 (4.8%) showed obstruction of the outflow tract (LVOT) with systolic anterior motion (SAM) of the mitral leaflet. In a multivariate analysis, the LVOT diameter (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.30-0.67; P < 0.001), transvalvular velocity (OR, 2.44; 95% CI, 1.13-5.26; P = 0.023), and the presence of accelerated intraventricular flow at baseline (OR, 6.13; 95% CI, 1.49-25.2; P = 0.012) were associated with the occurrence of LVO. Postprocedural LVO was not associated with midterm all-cause death or heart failure events. CONCLUSION: In patients who underwent TAVI, MVO occurred more often than LVOT obstruction. However, the occurrence of postprocedural LVO was not associated with worsened clinical outcomes in these patients.

Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM). BACKGROUND: LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction. METHODS: Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS). RESULTS: Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively. Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies. CONCLUSIONS: Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM.

Right ventricular outflow tract obstruction in complicated monochorionic twin pregnancy.

OBJECTIVES: Severe right ventricular outflow tract obstruction (RVOTO) is a potential complication in recipient twins of twin-to-twin transfusion syndrome (TTTS) that requires postnatal follow-up or treatment. We aimed to evaluate pregnancy characteristics of neonates with RVOTO from complicated monochorionic twin pregnancies, determine the incidence of RVOTO in TTTS cases and construct a prediction model for its development. METHODS: This was an observational cohort study of all complicated monochorionic twin pregnancies with a postnatal diagnosis of RVOTO examined at our center. Cases were referred for evaluation of the need for fetal therapy or intervention because of TTTS, selective intrauterine growth restriction (sIUGR) or multiple congenital malformations in one of the twins. Ultrasound data were retrieved from our monochorionic twin database. Among liveborn TTTS recipients treated prenatally with laser therapy, those with RVOTO were compared with those without RVOTO (controls). We describe four additional cases with RVOTO that were not TTTS recipients. RESULTS: A total of 485 twin pregnancies received laser therapy for TTTS during the study period. RVOTO was diagnosed in 3% (11/368) of liveborn TTTS recipients, of whom two showed mild Ebstein's anomaly. Before laser therapy, pericardial effusion was seen in 45% (5/11) of RVOTO cases (P < 0.01) and abnormal A-wave in the ductus venosus (DV) in 73% (8/11) (P = 0.03), significantly higher proportions than in controls. Mean gestational age at laser therapy was 17 + 3 weeks in RVOTO cases compared with 20 + 3 weeks in controls (P = 0.03). A prediction model for RVOTO was constructed incorporating these three significant variables. One TTTS donor had RVOTO after the development of transient hydrops following laser therapy. Three larger twins in pregnancies complicated by sIUGR developed RVOTO, the onset of which was detectable early in the second trimester. CONCLUSIONS: RVOTO occurs in TTTS recipient twins but can also develop in TTTS donors and larger twins of pregnancies complicated by sIUGR. Abnormal flow in the DV, pericardial effusion and early gestational age at onset of TTTS are predictors of RVOTO in TTTS recipients, which suggests increased vulnerability to hemodynamic imbalances in the fetal heart in early pregnancy. These findings could guide diagnostic follow-up protocols after TTTS treatment. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US melody valve investigational device exemption trial.

BACKGROUND: Studies of transcatheter pulmonary valve (TPV) replacement with the Melody valve have demonstrated good short-term outcomes, but there are no published long-term follow-up data. METHODS AND RESULTS: The US Investigational Device Exemption trial prospectively enrolled 171 pediatric and adult patients (median age, 19 years) with right ventricular outflow tract conduit obstruction or regurgitation. The 148 patients who received and were discharged with a TPV were followed up annually according to a standardized protocol. During a median follow-up of 4.5 years (range, 0.4-7 years), 32 patients underwent right ventricular outflow tract reintervention for obstruction (n=27, with stent fracture in 22), endocarditis (n=3, 2 with stenosis and 1 with pulmonary regurgitation), or right ventricular dysfunction (n=2). Eleven patients had the TPV explanted as an initial or second reintervention. Five-year freedom from reintervention and explantation was 76±4% and 92±3%, respectively. A conduit prestent and lower discharge right ventricular outflow tract gradient were associated with longer freedom from reintervention. In the 113 patients who were alive and reintervention free, the follow-up gradient (median, 4.5 years after implantation) was unchanged from early post-TPV replacement, and all but 1 patient had mild or less pulmonary regurgitation. Almost all patients were in New York Heart Association class I or II. More severely impaired baseline spirometry was associated with a lower likelihood of improvement in exercise function after TPV replacement. CONCLUSIONS: TPV replacement with the Melody valve provided good hemodynamic and clinical outcomes up to 7 years after implantation. Primary valve failure was rare. The main cause of TPV dysfunction was stenosis related to stent fracture, which was uncommon once prestenting became more widely adopted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00740870.

Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy.

PURPOSE: Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. METHODS: We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. RESULTS: Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. CONCLUSION: Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd.

[BICUSPID AORTIC VALVE AND LEFT VENTRICULAR OUTFLOW TRACT DEFECTS IN CIIILDREN - SYNDROME OF BICUSPID AORTOPATHY?]. / BIKUSPIDALNA AORTALNA VALVULA I GRJESKE IZLAZNOG TRAKTA LIJEVE KLIJETKE U DJECE - SINDROM BIKUSPIDALNE AORTOPATIJE?

UNLABELLED: Although bicuspid aortic valve (BAV) is considered the most common congenital heart defect (CHD) in adult age, with the 0.5-2% prevalence, BAV is not part of epidemiological studies of congenital heart defects (CHD) in children. Aortic valvulogenesis disorder is part of the left ventricular outflow tract (LVOT) genetic disorders which include: hypoplastic left heart syndrome (HLHS), aortic stenosis (AS) and insufficiency (AI), dilatation of the ascending aorta (DAA), coaretation of the aorta (CoA), Shone's syndrome (SS), and probably some other disorders. Our observations indicate that BAV related significant pathologic and hemodynamic changes occur in children already. In an 11-year long retrospective study (2000-2011) we have found 229 BAV patients, predominantly males (1.7). The most common BAV associated disorder was CoA (75 patients, 32.6%). Of all the children with BAV, 62.4% (143:229) had hemodynamic alterations on the aortic valve which manifested themselves as aortic stenosis and/or insufficiency. AS is mostly progressive and becomes hemodynamically relevant in childhood age already, while AI is mostly mild and rarely hemodynamically relevant. A large proportion of patients had isolated AS with DAA (21 or 14.7%), while most patients had combined AS and AI (29 or 20.3%). Due to morphological changes on the valve itself and on the adjoining defects, numerous interventional and cardiosurgical procedures have been performed. Their number has been growing with age, in accordance with the expected progression of pathological changes on the valve (AS, AI) or on the aorta (DAA). DAA in children with BAV was found in 76 (33.2%) patients, in various combinations with other associated LVOT anomalies. Already in childhood have the following surgical procedures on children with primary BAV diagnosis been performed : resection of CoA with T-T anastomosis was performed in 56 patients (24.5%); balloon aortic valvuloplasty in 28 patients (12.3%); commissurotomy in 19 patients (8.3%); balloon dilatation of CoA in 15 patients (6.5%); subaortic membrane resection in 11 patients (4.8%); Ross procedure in 8 patients (3.5%); resection of CoA with reconstruction in 8 patients (3.5%); valvuloplasty in 6 patients (2.6%); ascending aortoplasty in 5 patients (2.2%); mechanical valve replacement in 3 patients (1.3%); "subclavian flap" in 3 patients (1.3%); biological aortic valve replacement in 2 patients (0.9%); Bentall procedure in 1 patient (0.4%); David procedure in 1 patient (0.4%). CONTRIBUTION OFTHE STUDY: A BAV finding in children is a predictive factor for a progressive development of morphological changes in various LVOT parts, requiring that in some patients hemodynamic repercussions be removed already in childhood. CONCLUSION: The term valvular aortopathy, that is bicuspid aortic valve syndrome, should be in use already for children, and the anomaly should be included in epidemiological CHD research.

Coronary artery compression during intention to treat right ventricle outflow with percutaneous pulmonary valve implantation: incidence, diagnosis, and outcome.

OBJECTIVES: Evaluate the incidence, diagnosis, and outcome of coronary compression (CC) during right-ventricular outflow tract interventions. BACKGROUND: The incidence, risk factors, diagnosis, and outcomes of CC during percutaneous pulmonary valve implantation are poorly defined. METHODS: One-hundred consecutive patients (May 2008 to January 2012) undergoing transcatheter right-ventricular outflow tract treatment in two institutions were studied. RESULTS: CC occurred in six patients (6%) with a right ventricular outflow conduit stenosis, at a median age of 24.5 (13-49) years. It involved the left main coronary artery in four and the right coronary artery originating from the left anterior descending coronary artery in two patients. Conduit types were homograft (n = 3), bioprosthesis (n = 2), and a pericardial patch (n = 1). Median diameter was 23 (17-24) mm at surgical implantation. CC was diagnosed through a selective coronary angiogram during balloon dilation of the conduit in the first three patients and through an aortic root angiogram for the three next cases because we recognized that proximal compression could be masked during coronary artery cannulation. It was suspected on pre-procedure imaging (magnetic resonance imaging and/or computed tomography) in three cases. Patients with abnormal coronary anatomy tend to be at increased risk of CC (P = 0.0504). One institution had a higher incidence of CC (P = 0.04). CC resolved after balloon deflation. No patient underwent conduit stenting. Four patients underwent surgical reconstruction of right ventricular outflow tract. CONCLUSIONS: CC is accurately diagnosed during right-ventricular outflow tract interventions. We recommend an aortic root angiogram during dilation with a non-compliant balloon matching the diameter and length of the intended conduit implant.

Association between maternal body mass index and congenital heart defects in offspring: a systematic review.

The aim of this study was to investigate the relationship between maternal body mass index and all congenital heart defects (CHDs) combined and 11 individual defects. PubMed, ELSEVIER ScienceDirect, and Springer Link (up to February 2013) were searched, and the reference list of retrieved articles was reviewed. Three authors independently extracted the data. The systematic review included 24 studies, 14 of which were included in a metaanalysis. Statistical software was used to perform all statistical analyses. Fixed-effects or random-effects model was used to pool the results of individual study (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]). A dose-response effect was observed between overweight, moderate obesity, and severe obesity and a pregnancy with any CHD (the pooled ORs: OR, 1.08 [95% CI, 1.02-1.15]; OR, 1.15 [95% CI, 1.11-1.20]; and OR, 1.39 [95% CI, 1.31-1.47], respectively) as well as some individual defects such as hypoplastic left heart syndrome, pulmonary valve stenosis, and outflow tract defects. When we excluded mothers with diabetes mellitus, the pooled ORs for all CHDs combined were 1.12 (95% CI, 1.04-1.20) and 1.38 (95% CI, 1.20-1.59) for moderately obese and severely obese, respectively. The highest increased risk was severely obese mothers for tetralogy of Fallot (OR, 1.94; 95% CI, 1.49-2.51). Being underweight did not increase the risk of any of the aforementioned CHDs but did increase the risk of aortic valve stenosis (OR, 1.47; 95% CI, 1.01-2.15]). The results of our study showed that increasing maternal body mass index was associated with an increasing risk of CHDs; severe obesity was an even greater risk factor for the development of CHDs.

Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience.

BACKGROUND: Some patients with Takotsubo cardiomyopathy (TTC) develop cardiogenic shock due to left ventricular outflow tract (LVOT) obstruction - there is, however, a paucity of data regarding this condition. METHODS: Prevalence, associated factors and management implications of LVOT obstruction in TTC was explored, based on two-year data from two Belgian heart centres. RESULTS: A total of 32 patients with TTC were identified out of 3,272 patients presenting with troponin-positive acute coronary syndrome. In six patients diagnosed with TTC (19%), a significant LVOT obstruction was detected by transthoracic echocardiography. Patients with LVOT obstruction were older and had more often septal bulging, and presented more frequently in cardiogenic shock as compared to those without LVOT obstruction (P < 0.05). Moreover, all patients with LVOT obstruction showed systolic anterior motion (SAM) of the anterior mitral valve leaflet, which was associated with a higher grade of mitral regurgitation (2.2±0.7 vs. 1.0±0.6, P<0.001). Adequate therapeutic management including fluid resuscitation, cessation of inotropic therapy, intravenous ß-blocker, and the use of intra-aortic balloon pump resulted in non-inferior survival in TTC patients with LVOT obstruction as compared to those without LVOT obstruction. CONCLUSIONS: TTC is complicated by LVOT obstruction in approximately 20% of cases. Older age, septal bulging, SAM-induced mitral regurgitation and hemodynamic instability are associated with this condition. Timely and accurate diagnosis of LVOT obstruction by echocardiography is key to successful management of these TTC patients with LVOT obstruction and results in a non-inferior outcome as compared to those patients without LVOT obstruction.

Radiofrequency catheter ablation for the treatment of idiopathic premature ventricular contractions originating from the right ventricular outflow tract: a systematic review and meta-analysis.

BACKGROUND: Frequent idiopathic premature ventricular contractions (PVCs) have been associated with left ventricular cardiomyopathy. Idiopathic PVCs often originate from the right ventricular outflow tract (RVOT), and radiofrequency catheter ablation (RFCA) is being used as a treatment to alleviate symptoms. A meta-analysis was performed to evaluate RFCA for the treatment of frequent idiopathic PVCs on heart function. METHODS AND RESULTS: A literature search was conducted using Medline and Embase to identify studies evaluating the effects of RFCA as treatment for PVCs originating from the RVOT. Articles were chosen if they reported the effect of RFCA on the quantity of PVCs or ventricular function. Only studies in English were included. Articles were excluded if they did not separate results for PVCs originating from areas other than the RVOT. A total of 450 articles were retrieved from electronic searches, and 14 articles were included in this systematic review. Six of these were meta-analyzed (N = 70) and showed a reduction in the total number of PVCs in 24 hours after RFCA by a mean of -30089.44 confidence interval [CI]: -31658.47, -28520.40, P < 0.00001). Left ventricular ejection fraction (LVEF) was reported in five of the 14 studies, which included 108 patients. RFCA significantly improved LVEF by a mean of 10.36 (CI: 8.75, 11.97, P < 0.00001) in patients with frequent PVCs from the RVOT. The remaining studies reported their results differently and were not included in the meta-analyses but were described separately. CONCLUSIONS: RFCA reduces the number of PVCs and improves the cardiac function in patients with idiopathic frequent PVCs originating from the RVOT.

Angiotensinogen gene variations and LV outflow obstruction in hypertrophic cardiomyopathy.

BACKGROUND: Variations of angiotensinogen (AGT) gene have been associated with cardiac hypertrophy. We hypothesized that AGT gene polymorphism may play a modifier role in the diversity of left ventricular outflow obstruction. METHODS: The polymorphisms of the AGT gene were genotyped in 225 patients with hypertrophic cardiomyopathy (HCM) and 243 age-and sex-matched healthy controls. The effect of the A and G alleles on the expression of the reporter gene were evaluated in vitro using dual-luciferase reporter assays. RESULTS: Our results showed that the frequency of the A allele was higher in patients than in controls (50.2 % vs. 35.8 %, p < 0.05). Patients carrying the AA and AG genotypes had a higher proportion of left ventricular outflow obstruction (30.1 % vs. 17.0 %, p < 0.05) and heart failure (NYHA functional class III ~ IV, 35.4 % vs. 18.8 %, p < 0.05) than those carrying the GG genotype had. After adjusted for age, sex, the thickness of the interventricular septum, family history of HCM, and sudden death, the A allele conferred a 2.4-fold risk for left ventricular outflow obstruction than the GG genotype did (adjusted OR = 2.4, 95 %CI 1.2-4.8). The G allele suppressed the expression of the reporter gene significantly compared with the A allele (p < 0.05). CONCLUSION: AGT gene variations may be genetic modifiers for the development of HCM.

Risk factors in the origin of congenital left-ventricular outflow-tract obstruction defects of the heart: a population-based case-control study.

The aim of our project was to study possible etiological factors in the origin of congenital heart defects (CHDs) because in the majority of patients the underlying causes are unclear. Cases with different CHD entities as homogeneously as possible were planned for evaluation in the population-based large data set of the Hungarian Case Control Surveillance of Congenital Abnormalities. Dead or surgically corrected 302 live-born cases with different types of left-ventricular outflow tract obstructive defects (LVOT, i.e., valvular aortic stenosis 76, hypoplastic left heart syndrome 76, coarctation of the aorta 113, and other congenital anomalies of aorta 32) were compared with 469 matched controls, 38,151 controls without any defects, and 20,750 malformed controls with other isolated defects. Medically recorded pregnancy complications and chronic diseases were evaluated based on prenatal maternity logbooks, whereas acute diseases, drug treatments, and folic acid/multivitamin supplementation were analyzed both on the basis of retrospective maternal information and medical records. The results of the study showed the role of maternal diabetes in the origin of LVOT in general, while panic disorder was associated with a higher risk of hypoplastic left heart syndrome and ampicillin treatment with a higher risk of coarctation of the aorta (COA). High doses of folic acid had a protective effect regarding the manifestation of LVOT, particularly COA. In conclusion, only a minor portion of causes was shown in our study; thus, further studies are needed to understand better the underlying causal factors in the origin of LVOT.

Periconceptional paternal smoking and the risk of congenital heart defects: a case-control study.

BACKGROUND: Maternal smoking during pregnancy has been consistently associated with an increased risk of congenital heart defects (CHDs). However, few studies have reported the association between paternal smoking during pregnancy and CHDs among offspring. This report presents the first case-control study to investigate the possible association between periconceptional paternal smoking and CHDs in China. METHODS: From February 2010 through October 2011, 284 case fetuses with nonsyndromic CHDs and 422 control fetuses with no birth defects were recruited. The mothers of cases and controls were interviewed regarding whether the fathers of fetuses smoked and avoided the mothers while smoking during the periconceptional period. An unconditional logistic regression was used to calculate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS: Light paternal smoking increased the risk of isolated conotruncal heart defects (AOR, 2.23; 95% CI, 1.05, 4.73). Medium paternal smoking seemed to be associated with septal defects (AOR, 2.04; 95% CI, 1.05, 3.98) and left ventricular outflow tract obstructions (AOR, 2.48; 95% CI, 1.04, 5.95). Heavy paternal smoking was also associated with isolated conotruncal heart defects (AOR, 8.16; 95% CI, 1.13, 58.84) and left ventricular outflow tract obstructions (AOR, 13.12; 95% CI, 2.55, 67.39). Paternal smoking with no avoidance behavior was associated with an increased risk of these CHDs subtypes. CONCLUSIONS: Periconceptional paternal smoking increased the risk of isolated conotruncal heart defects, septal defects and left ventricular outflow tract obstructions. The avoidance behavior of paternal smokers may decrease the risk of selected CHDs.

Effects of sex on clinical outcomes of hypertrophic cardiomyopathy in Singapore.

Introduction: Despite the growing recognition that sex can affect the presentation and outcomes in hypertrophic cardiomyopathy (HCM), this relationship is understudied in Asians. Therefore, we aimed to explore sex differences in Asian patients with HCM. Method: A total of 295 consecutive patients diagnosed with HCM were recruited from a tertiary cardiology centre from 2010 to 2017 over a mean of 3.9±2.7 years. We evaluated the effects of sex on the outcomes of HCM in Asian patients. Results: HCM patients were more commonly men (72%). Women were older and had more comorbidities, including hypertension and atrial fibrillation. On transthoracic echocardiography, the indexed left ventricular end-systolic and end-diastolic volumes were similar, but more women had more-than-moderate mitral regurgitation and had a smaller left ventricular outflow tract (LVOT). Women more commonly had findings of obstructive physiology with significant LVOT obstruction, defined as >30 mmHg at rest. The use of implantable cardioverter defibrillators was similar across sexes. On multivariable analysis, women were found to be more likely to develop progressive heart failure requiring admission (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.05-4.71, P=0.021) but had a lower rate of all-cause mortality (HR 0.36, 95% CI 0.19-0.70, P=0.003). Conclusion: Women diagnosed with HCM were older, had more comorbidities and were more likely to develop heart failure while men had a higher risk of all-cause mortality.

Surgical correction for sinus of valsalva aneurysm with right ventricular outflow tract stenosis.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly, and SVA combined with right ventricular outflow tract stenosis is even rarer. We retrospectively analyzed 222 patients receiving surgical repair of SVA in our center over nine years, and report the incidence of right ventricular outflow tract stenosis in SVAs and the surgical results of 13 cases of SVA with right ventricular outflow tract stenosis. METHODS: Between January 2000 and December 2009, 13 patients with SVA combined with right ventricular outflow tract stenosis underwent surgical repair of SVA and correction of right ventricular outflow tract stenosis. There were nine males and four females. The mean age was 29.69 ± 9.98 years (range 13 to 45 years). Associated cardiovascular lesions were ventricular septal defect (n = 12), aortic regurgitation (n = 9), mitral regurgitation (n = 2), and tricuspid regurgitation (n = 1). All 13 patients were followed from 35 to 126 months (mean 80.15 ± 32,14 months). RESULTS: There was neither early death after operation nor late death. All the patients recovered well uneventfully. The incidence of right ventricular outflow tract stenosis among 222 SVA patients was 5.86%. CONCLUSIONS: Surgical correction of SVA with right ventricular outflow tract stenosis results in good mid-term results. Longer follow-up is needed to determine the efficacy of this procedure as this cohort of patients ages.

Incidence and management of the left ventricular outflow obstruction in patients with atrioventricular septal defects.

OBJECTIVES: Left ventricular outflow tract obstruction (LVOTO) is a recognized complication after complete repair of atrioventricular septal defect (AVSD). This study reviewed the incidence and management of LVOTO following AVSD repair at a single institution. METHODS: From 1975 to 2019, 24 patients (3.3%, 24/730) underwent reoperation due to LVOTO following partial AVSD (pAVSD) and complete AVSD (cAVSD) repair. The data were retrospectively reviewed. RESULTS: The incidence of LVOTO following pAVSD and cAVSD repair was 4.4% (12/275) and 2.6% (12/455). Freedom from LVOTO reoperation following pAVSD and cAVSD repair at 25 years was 94.3% [95% confidence interval (CI); 89.7-96.7] and 95% (95% CI; 91.1-97.3). The median time from complete repair of pAVSD and cAVSD to LVOTO reoperation was 4.4 years [interquartile range (IQR): 3.4-6.7] and 2.6 years (IQR: 2.2-4.7). Freedom from second LVOTO reoperation at 5, 10 and 15 years was 83.7% (95% CI; 57.2-98.2), 59.2% (95% CI; 28.7, 80.3) and 39.5% (95% CI; 13.2-65.3). The median time between the first and the second LVOTO reoperation in the groups of pAVSD and cAVSD was 6.1 years (IQR: 3.4-8.9) and 8.6 years (IQR: 5.7-9.8). There was no significant difference regarding the first (P = 0.7406) and subsequent LVOTO (P = 0.7153) following complete repair of pAVSD and cAVSD. Combined access to the left ventricular outflow tract was not protective regarding LVOTO reoccurrence. Survival for both groups after LVOTO reoperation at 15 years was 95.6% (95% CI 99.4-72.9). CONCLUSIONS: Incidence of LVOTO after AVSD repair is low but the reoccurrence rate is high. Standard subaortic resection does not always provide definitive LVOTO relief. The survival after LVOTO reoperation is excellent.

Cryopreserved homograft in the Ross procedure: outcomes and prognostic factors.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the dynamics and risk factors related to cryopreserved homografts implanted to reconstruct the right ventricular outflow tract (RVOT) during the Ross procedure. METHODS: A retrospective study, conducted between 1993 and 2009, included 107 consecutive patients who underwent a Ross procedure with implantation of a homograft (102 pulmonary, five aortic). The median patient age at implant was 18.8 years (range: 2 months - 67 years). The main cardiac defects were congenital aortic stenosis (n = 44), congenital aortic regurgitation (n = 20), and combined (n = 23) and acquired (n = 20) aortic regurgitation. The study endpoints were homograft stenosis (peak gradient > or = 20 mmHg), regurgitation (grade > or = moderate), homograft dysfunction (stenosis > or = 50 mmHg or regurgitation > or = moderate), homograft explant, and failure (explant or balloon dilation). The mean follow up was 5.7 +/- 0.4 years. The statistical analysis was conducted using univariate and multivariate Cox regression tests. RESULTS: The overall patient survival was 97% at 18 years. Homograft stenosis occurred in 54% of patients, regurgitation in 18%, dysfunction in 27%, explant in 5%, and failure in 6%. Freedom from homograft dysfunction was 75% and 55% at five and 10 years, respectively, while freedom from homograft failure was 99% and 84% at five and 10 years, respectively. The main multivariate risk factors for dysfunction were: homograft diameter < 22 mm (OR: 11, p = 0.019), aortic homograft (OR: 18, p = 0.019) and preoperative right ventricle/left ventricle pressure ratio > 0.4 (OR: 5, p = 0.018). Univariate risk factors for failure were: homograft diameter < 22 mm (p = 0.006), donor age < 30 years (p = 0.03), cold ischemia time < 2 days (p = 0.04), and decontamination time < 12 h (p = 0.01). CONCLUSION: In the Ross procedure, the cryopreserved homograft represents an excellent means to reconstruct the RVOT, with a good long-term longevity. Almost 85% of patients did not require any surgery or percutaneous intervention at 10 years after implantation. The homograft long-term durability depends on both homograft-related and patient-related factors. Pulmonary homografts, with a diameter > 22 mm, a donor age > 30 years, and a cold ischemia time > 2 days are to be preferred.