Exercise test in patients with asymptomatic aortic stenosis: clinically useful or not?

INTRODUCTION: Aortic valve replacement (AVR) is recommended for symptomatic patients with severe aortic stenosis (AS). In asymptomatic AS (AAS), exercise testing (ET) is recommended; however, it remains controversial. OBJECTIVES: The aim of our study was to assess the importance of ET in patients with AAS. PATIENTS AND METHODS: A total of 89 patients with AAS (53 men; mean [SD] age, 59.5 [11.7] years) underwent 244 symptom­limited ETs. RESULTS: All ETs were clinically negative. During the median (interquartile range) follow­up of 22 (12) months, 39 patients (22 men) developed symptoms (the AVR group). This group was compared with 50 asymptomatic non­AVR patients. In the multivariable Cox analysis, the maximal heart rate during ET less than 85% of age- and sex-adjusted maximal predicted heart rate (THR less than 85%) was related to AVR (P = 0.01). After adjusting for the use of ß­blockers, this was not significant (P = 0.08). In the ß­blocker subgroup, the THR less than 85% was significantly related to AVR in the univariable Cox analysis (hazard ratio, 2.2; 95% CI, 1.07-4.9; P = 0.03) and after adjusting for age (P = 0.047). This relationship was not observed in patients who did not receive ß­blockers. CONCLUSION: In patients with AAS, ET is safe; however, in our study group, the results were not cru­ cial in making a decision to perform AVR. Patients treated with ß­blockers who did not achieve 85% of predicted maximal heart rate had a higher probability of AVR. The influence of the use of ß­blockers on the decision to perform AVR in this patient population warrants further revision.

Asymmetric multiscale multifractal analysis (AMMA) of heart rate variability.

Objective.The physiological activity of the heart is controlled and modulated mostly by the parasympathetic and sympathetic nervous systems. Heart rate variability (HRV) analysis is therefore used to observe fluctuations that reflect changes in the activity in these two branches. Knowing that acceleration and deceleration patterns in heart rate fluctuations are asymmetrically distributed, the ability to analyze HRV asymmetry was introduced into MMA.Approach. The new method is called asymmetric multiscale multifractal analysis (AMMA) and the analysis involved six groups: 36 healthy persons, 103 cases with aortic valve stenosis, 36 with hypertrophic cardiomyopathy, 32 with atrial fibrillation, 59 patients with coronary artery disease (CAD) and 13 with congestive heart failure.Main results. Analyzing the results obtained for the 6 groups of patients based on the AMMA method, i.e. comparing the Hurst surfaces for heart rate decelerations and accelerations, it was noticed that these surfaces differ significantly. And the differences occur in most groups for large fluctuations (multifractal parameterq > 0). In addition, a similarity was found for all groups for the AMMA Hurst surface for decelerations to the MMA Hurst surface-heart rate decelerations (lengthening of the RR intervals) appears to be the main factor determining the shape of the complete Hurst surface and so the multifractal properties of HRV. The differences between the groups, especially for CAD, hypertrophic cardiomyopathy and aortic valve stenosis, are more visible if the Hurst surfaces are analyzed separately for accelerations and decelerations.Significance. The AMMA results presented here may provide additional input for HRV analysis and create a new paradigm for future medical screening. Note that the HRV analysis using MMA (without distinguishing accelerations from decelerations) gave satisfactory screening statistics in our previous studies.

Brain natriuretic peptide as a marker of left ventricular hypertrophy in patients with aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: In aortic stenosis (AS), serum levels of brain natriuretic peptide (BNP) are elevated, but the relation of this elevation to the degree of left ventricular hypertrophy (LVH) remains unclear. The study aim was to assess the relationship between BNP and LVH (expressed as LV mass index, LVMI) and LV wall thickness index (WThI) in a group of patients. METHODS: A total of 147 patients with AS (85 men, 62 women; mean age 61 +/- 12 years) each underwent echocardiography and serum BNP analysis. The correlation between serum BNP level and LVH was investigated, with patient gender, age, NYHA class, AS severity and presence of coronary artery disease also being taken into account. RESULTS: Among AS patients, serum BNP levels ranged from 3 to 2010 pg/ml; mean BNP levels were similar in women and men (213 +/- 302 and 253 +/- 375 pg/ml, respectively). The BNP level also correlated directly with the LVMI (r = 0.55; p <0.0001), WThI (r = 0.26; p <0.001), end-diastolic dimension (r = 0.43; p <0.0001), mean aortic gradient (r = 0.25; p = 0.002), age (r = 0.27; p = 0.001); and correlated inversely with the LV ejection fraction (r = -0.52; p <0.0001). Eccentric LVH was associated with a significantly higher serum BNP level (506 +/- 558 pg/ml) than concentric-type hypertrophy (190 +/- 254 pg/ml; p = 0.002). CONCLUSION: The measurement of serum BNP levels is of potential value when monitoring LVH in aortic stenosis patients.

Heart rate variability, multifractal multiscale patterns and their assessment criteria.

OBJECTIVE: Both the central nervous system and the autonomic nervous system are complex physiological networks which modulate the heart rate. They are spatially extended, have built-in delays and work on many time scales simultaneously-nonhomogeneous networks with multifractal dynamics. The object of our research was the analysis of human heart rate variability (HRV) using the nonlinear multiscale multifractal analysis (MMA) method for several cardiovascular diseases. The analysis of HRV (night-time recordings) involved six groups of patients: 61 healthy persons, 104 cases with aortic valve stenosis, 42 with hypertrophic cardiomyopathy, 36 with atrial fibrillation, 70 patients with coronary artery disease and 19 with congestive heart failure. 85% of patients formed a training data set (282 subjects) and 15% formed a test data set (50 subjects). APPROACH: Multiscale multifractal analysis allows one to analyze the complexity of HRV and find the scaling properties of its fluctuations. The main result of MMA is the Hurst surface, the shape of which changes depending on the medical case analyzed. We prepared six criteria to distinguish a multifractal pattern for healthy subjects. We also prepared additional criteria, enabling one to recognize atrial fibrillation. MAIN RESULTS: For the training data set, we obtained the following accuracy statistics in distinguishing the patients from the healthy: 68% for coronary artery disease, 67% for hypertrophic cardiomyopathy, 88% for atrial fibrillation, 74% for aortic valve stenosis and 83% for congestive heart failure. For the complete training data set we obtained an accuracy of 73%, and 80% for the test data set (mean for ten random selections of the test data set). SIGNIFICANCE: The results of MMA presented here provide an additional input into the diagnostic process and may help to create a paradigm for future studies on medical screening methods, especially in that MMA focuses on very low frequencies of HRV not easily accessible by standard medical techniques. Satisfactory statistics for screening using both MMA and the unfiltered version of LF/HF indicate that the nature of the complete network moderating heart rhythm needs to be studied and that sinus rhythm in clinical patients may not always be separated from arrhythmia when its incidence is large.

Predictors of aortic stenosis severity reclassification using an imaging data fusion method in patients referred for transcatheter aortic valve implantation.

BACKGROUND: The use of imaging data fusion method (IDFM) with multislice computed tomography (MSCT) and two-dimensional transthoracic echocardiography (2D-TTE) in patients with aortic stenosis (AS) may result in reclassification of AS severity from severe to non-severe. AIM: We sought to establish potential predictors of AS severity reclassification using the IDFM method. METHODS: A total of 54 high-risk patients (mean age 79 ± 7.9 years; 40.7% male) with severe AS by 2D-TTE (indexed aortic valve area [AVAi] < 0.6 cm2/m2), referred for transcatheter aortic valve implantation, were included in the analysis. AVAi was subsequently recalculated using IDFM by replacing 2D-TTE left ventricular outflow tract (LVOT) measurements with MSCT LVOT parameters. RESULTS: Imaging data fusion method reclassified 20.4% patients into the potentially non-severe AS group. In a multivariable model including clinical variables, reclassification to non-severe AS by IDFM was independently associated with younger age and diabetes mellitus (DM), (odds ratio [OR] 0.864; 95% confidence interval [CI] 0.76-0.99; p < 0.035 and OR 19.259; 95% CI 2.28-162.41; p < 0.007, respectively). In a multivariable analysis of echocardiographic variables, reclassification was associ-ated with higher LVOT velocity time integral and lower aortic mean gradient (OR 1.402; 95% CI 1.07-1.84; p < 0.014 and OR 0.858; 95%: CI 0.760-0.968; p < 0.013, respectively). In addition, 24.1% of patients were reallocated from low-flow (< 35 mL/m2) to normal-flow AS. CONCLUSIONS: Imaging data fusion method reclassified a substantial proportion of patients with severe AS into a potentially moderate AS group and from a low-flow to a normal-flow AS group. Such regrouping calls for increased diagnostic prudence in AS patients, especially those with specific clinical and echocardiographic predictors of reclassification, such as DM or low aortic mean gradient.

Can angiotensin II +1675 G/A type 2 receptor gene polymorphism be a marker of left ventricular hypertrophy in patients with aortic stenosis?

BACKGROUND AND AIM OF THE STUDY: Activation of the angiotensin II type 2 receptor (AT2R) gene lowers blood pressure, inhibits endothelial and smooth muscle proliferation, and modifies left ventricular hypertrophy (LVH) and fibrosis. Recently, several studies on the presence and importance of AT2R polymorphism for cardiovascular pathology have been reported. The study aim was to investigate any relationship between +1675 G/A AT2R polymorphism and the degree of LVH in patients with aortic stenosis (AS). METHODS: The influence of +1675 G/A AT2R gene polymorphism on AS severity, degree of LVH and systolic function was analyzed in 308 patients (185 men, 123 women; mean age 61.5 +/- 10 years) with significant AS. RESULTS: Due to chromosome X localization of the AT2R gene, the analysis was performed separately in males and females. The prevalence of genotypes was 32.8% for AA, 40.8% for AG, and 26.4% for GG in females; and 52.9% and 47.1% for the A and G alleles, respectively, in males. No correlation was found between +1675 G/A AT2R polymorphism and LVH. The only significant difference was a lower left ventricular ejection fraction (LVEF) and a greater end-systolic LV dimension in males carrying the A allele as compared to allele G carriers. The A allele was more frequently observed in patients with LVEF < 40%. In the multivariate analysis, presence of the A allele was significantly related to LVEF (adjusted for age, hypertension, coronary artery disease), although the impact was of borderline statistical significance (p = 0.04) and explained only 2% of LVEF variance. CONCLUSION: The study results indicate that the +1675 G/A AT2R gene polymorphism cannot be considered as a marker of LVH in patients with AS, but its negative influence on LVEF in A allele carriers may be considered as a marker of premature left ventricular decompensation in males.

Early and long-term outcomes after surgical treatment in patients with aortic stenosis and severe left ventricular heart failure without concomitant coronary artery disease with respect to preoperative mean transvalvular pressure gradient.

INTRODUCTION: There are limited data on early and long-term prognosis in patients after aortic valve replacement who have left ventricular dysfunction, reduced ejection fraction (EF) < or =35% and no concomitant coronary artery disease. AIM: To assess the prognosis in this group of patients depending on the mean aortic gradient (MAG) value. METHODS: This study involved 60 patients with severe aortic stenosis and EF < or =35%. Patients with coronary artery disease, more than moderate aortic regurgitation and any other valvular lesion were excluded. Patients were divided into two groups based on the MAG values: group I included patients with MAG < or =35 mmHg, and group II included patients with MAG >35 mmHg. RESULTS: Early mortality after aortic valve replacement was 14.2% in group I, and 5.1% in group II. During a mean follow-up of 48 months mortality in groups I and II was 16.6% and 2.6%, respectively. In the follow-up period, a significant functional improvement according to NYHA scale as well as significant decrease of left ventricular dimensions and increase of EF was observed in both groups of patients. CONCLUSIONS: Patients with severe aortic stenosis, left ventricular ejection fraction <35% and MAG < or =35 mmHg constitute a group of the highest early and long-term mortality risk after valve replacement. In turn, patients with MAG >35 mmHg should be classified as the group of slightly increased risk.

Functional polymorphism of the renalase gene is associated with cardiac hypertrophy in female patients with aortic stenosis.

Renalase decreases circulating catecholamines concentration and is important in maintaining primary cellular metabolism. Renalase acts through the plasma membrane calcium ATPase 4b in the heart, which affects pressure overload but not exercise induced heart hypertrophy. The aim of this study was to test the association between a functional polymorphism Glu37Asp (rs2296545) of the renalase gene and left ventricular hypertrophy in a large cohort of patients with aortic stenosis. The study group consisted of 657 patients with aortic stenosis referred for aortic valve replacement. Preoperative echocardiographic assessment was performed to obtain cardiac phenotypes. Generalized-linear models were implemented to analyze data using crude or full model adjusted for selected clinical factors. In females, the Asp37 variant of the Glu37Asp polymorphism was associated with higher left ventricular mass (p = 0.0021 and p = 0.055 crude and full model respectively), intraventricular septal thickness (p = 0.0003 and p = 0.0143) and posterior wall thickness (p = 0.0005 and p = 0.0219) all indexed to body surface area, as well as relative wall thickness (p = 0.001 and p = 0.0097). No significant associations were found among the male patients. In conclusion, we have found the association of the renalase Glu37Asp polymorphism with left ventricle hypertrophy in large group of females with aortic stenosis. The Glu37Asp polymorphism causes not only amino-acid substitution in FAD binding domain but may also change binding affinity of the hypoxia- and hypertrophy-related transcription factors and influence renalase gene expression. Our data suggest that renalase might play a role in hypertrophic response to pressure overload, but the exact mechanism requires further investigation.

Raised red cell distribution width as a prognostic marker in aortic valve replacement surgery.

BACKGROUND AND AIM: Several studies have reported that elevated red cell distribution width (RDW) is associated with poor outcomes in patients with coronary artery disease, chronic heart failure and aortic stenosis following transcatheter aortic valve replacement. Their prognostic utility in patients undergoing aortic valve replacement (AVR) surgery is unknown. METHODS: We prospectively evaluated the prognostic value of RDW in a group of 191 consecutive patients with severe symptomatic aortic stenosis undergoing AVR. The pre-defined primary endpoint at the 30-day follow-up was composed of: all cause mortality, perioperative myocardial infarction, perioperative renal failure, prolonged mechanical ventilation, stroke, heart failure, successfully resuscitated cardiac arrest, the occurrence of multiple-organ failure, and the need for additional surgery for any reason. The secondary endpoint was total mortality. RESULTS: The composite endpoint occurred in 54 patients. In univariate analysis RDW (p < 0.0001), haemoglobin level (p = 0.005), haematocrit (p = 0.01), red blood cell count (RBC; p = 0.002), glomerular filtration rate (p = 0.003), New York Heart Association classification (p = 0.02), atrial fibrillation (p = 0.0044), and pulmonary blood pressure (p = 0.004) were associated with the occurrence of the composite endpoint. RDW (p = 0.0005), haemoglobin level (p = 0.004), haematocrit (p = 0.004), RBC (p = 0.0009) and mean corpuscular volume (p = 0.01) were associated with an increased risk of death. In multivariate analysis, RDW (OR 3.274; 95% CI 1.285-8.344; p = 0.0003) and RBC (OR 0.373; 95% CI 0.176-0.787; p = 0.0097) remained independent predictors of the composite endpoint. Receiver operating characteristic analysis determined a cut-off value of RDW for the prediction of the occurrence of the combined endpoint at 14.1%. CONCLUSIONS: Elevated RDW is associated with a worse outcome following AVR, independent of RBC.

Reduction of the QT interval dispersion after aortic valve replacement reflects changes in electrical function rather than structural remodeling.

BACKGROUND AND AIM OF THE STUDY: Factors related to changes of QT dispersion (QTd) after aortic valve replacement (AVR) in patients with aortic stenosis were analyzed. METHODS: The prospective group comprised 121 consecutive patients (45 women, 76 men; mean age 58 +/- 11 years; range: 24-77 years) with significant aortic valve stenosis. Data (clinical, echocardiographic and electrocardiographic) were collected before and at least 16 months after AVR. QTd was measured in the standard ECG. RESULTS: Before AVR, the mean QTd was 60 +/- 24 ms (QT(max) 424 +/- 40 ms). QTd was > 50 ms in 68% of patients, and > 70 ms in 30%. During postoperative follow up the mean QTd was 54 +/- 19 ms (QT(max) 368 +/- 36 ms) for all patients, and was > 50 ms in 58% of cases and > 70 ms in 13%. Postoperatively, QTd was decreased to < 70 ms in 27% of patients with a normalized left ventricular mass index (LVMI), and in 27% of those without any clinically significant reduction in left ventricular (LV) hypertrophy. In the multivariate analysis, QTd reduction was weakly related to the reduction in LV wall thickness (p = 0.09) and LVMI (p = 0.05). The reduction in QTd was more related to changes in T-wave amplitude in lead V5 (p = 0.004). CONCLUSION: Following AVR for aortic stenosis, a decrease in QTd was observed, notably among patients with QTd > 70 ms. This reduction was only weakly related to the degree of reduction in cardiac hypertrophy, but a more important relationship was observed with changes in T-wave amplitude. These findings suggest that a reduction in QTd after AVR is reflective of changes in electrical function rather than structural remodeling.

[Intravascular hemolysis after multiple valvular replacement procedures--a case report]. / Hemoliza u chorego po wielokrotnych operacjach wymiany sztucznej zastawki.

A case of an intravascular hemolysis after multiple aortic and mitral valves replacement is described. Hemolysis was observed after second and third operation of mitral valve prosthesis due to prosthesis dysfunction -- paravalvular leak. We discuss the possibilities of treatment, difficulties in decision making in a patient who is in good condition but hemolysis is clinically significant, not amenable to conventional treatment and there is an increased risk of another operation.

Aortic valve calcification in 499 consecutive patients referred for computed tomography.

INTRODUCTION: Aortic valve calcification (AVC) is the most common cause of aortic stenosis. The aim of the study was to assess the prevalence of aortic valve, coronary artery and aortic calcifications and to evaluate the correlation between calcification of the aortic valve, coronary arteries and aorta. MATERIAL AND METHODS: The study included 499 patients aged 60 years and over who underwent coronary computed tomography because of chest pain. Beside coronary artery calcium score (CAC), we evaluated AVC and ascending aorta calcifications (AAC). RESULTS: Aortic valve calcification was found in 144 subjects (28.9% of the whole study population). Prevalence of CAC and AAC was higher than AVC and amounted to 73.8% and 54.0%. Prevalence of AVC, CAC and AAC was significantly lower in the group of patients ≤ 70 years than in the group of patients > 70 years of age (p = 0.0002, p < 0.0001, p < 0.0001). Aortic valve calcification was more often observed in men than women (34.7% vs. 25.4%, p = 0.02). Degree of aortic valve calcification was also significantly higher among men than women (median score 4 vs. 0, p = 0.01). Similar observations were true for CAC and AAC, where both prevalence and degree of calcification was higher among men than women. In the whole study population no correlation was noted between AVC and CAC or AAC (p = 0.34, p = 0.85). There was a significant correlation between AAC and CAC (p < 0.0001). CONCLUSIONS: Despite some similarities in pathological mechanism and risk factors, a degenerative defect of the aortic valve could be independent of atheromatous lesions in the coronary arteries and aorta.

The impact of transcatheter aortic valve implantation on left ventricular performance and wall thickness - single-centre experience.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a treatment alternative for the elderly population with severe symptomatic aortic stenosis (AS) at high risk for surgical aortic valve replacement (SAVR). AIM: To assess the impact of TAVI on echocardiographic parameters of left ventricular (LV) performance and wall thickness in patients subjected to the procedure in a single-centre between 2009 and 2013. MATERIAL AND METHODS: The initial group consisted of 170 consecutive patients with severe AS unsuitable for SAVR. Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 21.73 ±12.42% and mean age was 79.9 ±7.5 years. RESULTS: The TAVI was performed in 167 (98.2%) patients. Mean aortic gradient decreased significantly more rapidly after the procedure (from 58.6 ±16.7 mm Hg to 11.9 ±4.9 mm Hg, p < 0.001). The LV ejection fraction (LVEF) significantly increased in both short-term and long-term follow-up (57 ±14% vs. 59 ±13%, p < 0.001 and 56 ±14% vs. 60 ±12%, p < 0.001, respectively). Significant regression of interventricular septum diameter at end-diastole (IVSDD) and end-diastolic posterior wall thickness (EDPWth) was noted in early (15.0 ±2.4 mm vs. 14.5 ±2.3 mm, p < 0.001 and 12.7 ±2.1 mm vs. 12.4 ±1.9 mm, p < 0.028, respectively) and late post-TAVI period (15.1 ±2.5 mm to 14.3 ±2.5 mm, p < 0.001 and 12.8 ±2.0 mm to 12.4 ±1.9 mm, p < 0.007, respectively). Significant paravalvular leak (PL) was noted in 21 (13.1%) patients immediately after TAVI and in 13 (9.6%) patients in follow-up (p < 0.001). Moderate or severe mitral regurgitation (msMR) was seen in 24 (14.9%) patients from the initial group and in 19 (11.8%) patients after TAVI (p < 0.001). CONCLUSIONS: The TAVI had an immediate beneficial effect on LVEF, LV walls thickness, and the incidence of msMR. The results of the procedure are comparable with those described in other centres.

Prediction of paroxysmal atrial fibrillation after aortic valve replacement in patients with aortic stenosis: identification of potential risk factors.

BACKGROUND AND AIM OF THE STUDY: Paroxysmal atrial fibrillation (AF) is a frequent complication after cardiac surgery. The study aim was to identify preoperative predictors of risk for this condition in patients with aortic stenosis after aortic valve replacement. METHODS: The influence of clinical, echocardiographic and 24 h electrocardiogram (ECG) parameters on episodes of paroxysmal AF after aortic valve replacement (AVR) in 423 patients (156 women, 267 men; mean age 58 +/- 10 years) with aortic stenosis was analyzed. Episodes of postoperative paroxysmal AF were noted in 120 patients (28%). RESULTS: Univariate analyses identified the following variables as risk factors for arrhythmia: age, NYHA functional class, history of preoperative paroxysmal AF, left ventricular mass index, >300 supraventricular beats on 24h ECG before surgery, presence of supraventricular tachycardia (SVT), SVT of >5 beats or with a rate >120 beats/min. Concomitant coronary artery bypass (CABG) grafting and presence of enlarged left atrium had no impact. By multivariate analysis, four variables were identified as independent predictors: age (odds ratio 1.7; 95% CI 1.2-2.1); history of paroxysmal AF (OR 3.2; CI 1.4-7.3); presence of >300 supraventricular beats/24 h (OR 1.9; CI 1.1-3.4); and presence of SVT (OR 2.1; CI 1.3-3.4). Discriminatory analysis revealed that a model comprising these four parameters enabled risk prediction in 68% of patients. CONCLUSION: In patients with isolated aortic stenosis, age, past history of paroxysmal AF episodes, >300 supraventricular beats/24 h and presence of SVT during 24 h before AVR were predictors of postoperative paroxysmal AF episodes. Left atrial diameter and simultaneous CABG during AVR did not influence the likelihood of postoperative paroxysmal AF.

QT interval dispersion analysis in patients with aortic valve stenosis: a prospective study.

BACKGROUND AND AIM OF THE STUDY: QT interval dispersion (QTd) was analyzed in patients with aortic valve stenosis, and the relationship investigated between QTd, age, gender, hypertension, presence of significant coronary artery stenosis and left ventricular (LV) hypertrophy assessed by echocardiography. Results were also compared between survivors and patients who had cardiac arrest or died before, during or soon after cardiac surgery. METHODS: The group comprised 535 consecutive patients (217 women, 318 men; mean age 59 +/- 11 years; range: 20-81 years) with significant aortic valve stenosis before valve replacement. The control group comprised 35 healthy subjects (12 women, 23 men; mean age 51 +/- 11 years; range: 28-74 years). RESULTS: Mean QTd was 29 +/- 10 ms in controls and 59 +/- 24 ms in patients (p < 0.001). Gender had no impact on QTd. QTd was increased in men with significant coronary artery stenosis, and independently related strongly with ECG parameters (QTmax, heart rate) and weakly with age and degree of LV hypertrophy. In patients with cardiac arrest or those who died (n = 14), QTd was increased compared to that in survivors (71 +/- 22 versus 59 +/- 24 ms; p = 0.05), and QTd >70 ms was observed more frequently (p = 0.02; odds ratio 3.4, 1.16-10.0). CONCLUSION: QTd is abnormally increased in two-thirds of patients with aortic valve stenosis, and is increased in men with concomitant coronary artery disease. QTd >70 ms significantly increased the risk of cardiac arrest or death perioperatively. QTd was only weakly related with age and degree of LV hypertrophy, but QTmax and heart rate had a greater impact. QT dispersion analysis has limited clinical value in patients with aortic stenosis.

Influence of ACE I/D genotypes on left ventricular hypertrophy in aortic stenosis: gender-related differences.

BACKGROUND AND AIM OF THE STUDY: Factors responsible for cardiac hypertrophy in patients with aortic stenosis (AS) are not well defined. The study aim was to examine the relationship between angiotensin-converting enzyme (ACE) I/D polymorphism and the degree of cardiac hypertrophy in patients with AS. METHODS: A total of 392 white patients (159 women, 233 men; age range: 32-82 years) with AS was analyzed, with clinical data, echocardiographic parameters and ACE I/D polymorphism being assessed. RESULTS: Left ventricular mass index (LVMI) and wall thickness (LVWT) were greater in men than in women (226 +/- 66 versus 200 +/- 68 g/m2, p <0.0001; and 28.4 +/- 4.5 versus 27.3 +/- 4.1 mm, p = 0.02, respectively). In all patients, LVMI was significantly correlated with the maximal aortic gradient, ejection fraction and gender, whereas LVWT was dependent upon maximal aortic gradient, ejection fraction, gender and history of hypertension. In women, cardiac hypertrophy increased with age. Hypertrophy in women aged <66 years correlated with an absence of the DD genotype. In men, a reverse correlation of both LVMI and LVWT with age was observed (higher in younger patients). The presence of a DD genotype in men seemed to have a significant impact on the degree of cardiac hypertrophy. CONCLUSION: The degree of left ventricular hypertrophy in patients with AS was higher in men than in women. ACE I/D polymorphism appeared to have a modulating impact on cardiac hypertrophy in patients with AS, notably those aged <66 years. A higher degree of cardiac hypertrophy was seen in men with the DD genotype, and in women without the DD genotype.

Incidence of syncope and cardiac arrest in patients with severe aortic stenosis.

INTRODUCTION:  Syncope and sudden cardiac arrest are known complications of aortic stenosis (AS). OBJECTIVES:  The aim of the study was to investigate the incidence of these complications in patients with severe symptomatic AS and to analyze whether basic clinical data and electrocardiographic (ECG) and echocardiographic parameters can be the markers of these complications. PATIENTS AND METHODS:  The incidence of syncope and sudden cardiac arrest and its correlations with clinical and diagnostic data (ECG, echocardiography, Holter monitoring) were analyzed in 514 patients (mean age, 60 ±11 y) with severe symptomatic AS before valve replacement. RESULTS:  Syncope was reported in 167 patients (32%), and aborted cardiac arrest in 14 (2.7%; ventricular fibrillation, 13 patients; third-degree atrioventricular block, 1 patient). None of the analyzed parameters was related to syncope. Patients with a history of sudden cardiac arrest had higher New York Heart Association class (P = 0.01), more frequent history of syncope (P = 0.017), higher left ventricular mass index (P = 0.02), lower ejection fraction (P = 0.004), longer QRS duration (P = 0.048), corrected QT (P = 0.002), QT dispersion (P = 0.007), and a higher number of ventricular arrhythmias in 24-hour Holter monitoring (P = 0.002). A multivariate analysis showed correlations between syncope, ejection fraction of less than 45%, and QTd exceeding 60 ms and aborted cardiac arrest. At least 2 of these parameters were observed in 8 of 14 patients (P <0.001): sensitivity, 57%; specificity, 86%; positive predictive value, 10%; and negative predictive value, 98%. CONCLUSIONS:  The incidence of sudden cardiac arrest in severe symptomatic AS is low. It is higher in patients with a history of syncope, prolongation of QTd, and reduced ejection fraction. None of the clinical and diagnostic parameters were associated with a history of syncope in patients with AS.

Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.

We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-ß activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84 × 10(-5)), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload.

Hypertension in aortic stenosis: more questions than answers.

Although hypertension and aortic stenosis are the most common cardiovascular diseases, the impact of hypertension on the natural history of aortic stenosis, the structure and function of the left ventricle, the assessment of valve defect severity and its progression are not fully understood. Hypertension not only can modify the exploratory findings of aortic stenosis, but may also interfere with the assessment of severity, and even have an impact on patients outcome. In the absence of specific cohort studies, the nature of the association between aortic stenosis and high blood pressure is not clear and the published results are often contradictory. Unknown is the true frequency of both conditions, the rules of diagnosis and the treatment itself.

Antithrombotic therapy - predictor of early and long-term bleeding complications after transcatheter aortic valve implantation.

INTRODUCTION: Dual antiplatelet therapy (DAPT) - aspirin and clopidogrel - is recommended after transcatheter aortic valve implantation (TAVI) without an evidence base. The main aim of the study was to estimate the impact of antithrombotic therapy on early and late bleeding. Moreover, we assessed the impact of patients' characteristics on early bleeding and the influence of bleeding on prognosis. MATERIAL AND METHODS: Between 2009 and 2011, 83 consecutive TAVI patients, age 81.1 ±7.2 years, were included. Bleeding complications were defined by the Valve Academic Research Consortium (VARC) scale. The median follow-up was 12 ±15.5 months (range: 1 to 23) and included 68 (81.9%) patients. RESULTS: Early bleeding occurred in 51 (61.4%) patients. Vitamin K antagonists (VKA) pre-TAVI (p = 0.001) and VKA + clopidogrel early post-TAVI (p = 0.04) were the safest therapies; in comparison to the safest one, peri-procedural DAPT (p = 0.002; p = 0.05) or triple anticoagulant therapy (TAT) (p = 0.003, p = 0.05) increased the risk for early bleeding. Predictors for early bleeding were: clopidogrel pre-TAVI (OR: 4.43, 95% CI: 1.02-19.24, p = 0.04), preceding percutaneous coronary intervention (PCI) (10.08, OR: 95% CI: 1.12-90.56, p = 0.04), anemia (OR: 4.00, 95% CI: 1.32-12.15, p = 0.01), age > 85 years (OR: 5.96, 95% CI: 1.47-24.13, p = 0.01), body mass index (BMI) (OR: 0.86, 95% CI: 0.74-0.99, p = 0.04). Late bleeding occurred in 35 patients (51.4%) on combined therapy, and none on VKA or clopidogrel monotherapy (p = 0.04). Bleeding complications did not worsen the survival. CONCLUSIONS: This study seems to suggest that advanced age, BMI, and a history of anemia increased the risk for early bleeding after TAVI. Clopidogrel pre-TAVI should be avoided; therefore, time of preceding PCI should take into account discontinuation of clopidogrel in the pre-TAVI period. Vitamin K antagonists with clopidogrel seems to be the safest therapy in the early post-TAVI period, similarly as VKA/clopidogrel monotherapy in long-term prophylaxis.