Risk Prediction Models and Scores in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has historically been linked with sudden cardiac death (SCD). Currently, it is well established that only a subset of patients is at the highest risk stratum for such a catastrophic event. Detection of patients belonging to this high-risk category can allow for timely defibrillator implantation, changing the natural history of HCM. Inversely, device implantation in patients deemed at low risk leads to an unnecessary burden of device complications with no apparent protective benefit. Previous studies have identified a series of markers, now considered established risk factors, with genetic testing and newer imaging allowing for the detection of novel, highly promising indices of increased risk for SCD. Despite the identification of a number of risk factors, there is noticeable discrepancy in the utility of such factors for risk stratification between the current American and European guidelines. We sought to systematically review the data available on these two approaches, presenting their rationale and respective predictive capacity, also discussing the potential of novel markers to augment the precision of currently used risk stratification models for SCD in HCM.

MitraClip device for patients with functional mitral valve regurgitation: A systematic review.

BACKGROUND: MitraClip device is a novel therapeutic option for patients with degenerative mitral valve regurgitation. Nevertheless, several studies have also focused on the safety and efficacy of this method in functional mitral valve regurgitation (FMR). AIM: To systematically review all original studies that provided mortality data among FMR patients treated with MitraClip. MATERIALS AND METHODS: We conducted an in-depth literature search of 3 electronic databases (Medline, Scopus and Cochrane Library) in order to identify studies investigating the efficacy of MitraClip in FMR. Thirty-day and 12-month mortality after MitraClip implantation were the measured outcomes. RESULTS: Twenty-eight studies, involving 2383 patients, were included. The phenotype of the studied population was characterized by clinical and echocardiographic parameters suggesting severe FMR (NYHA III-IV: 91%, MR≥3+: 98%) with high surgical risk (mean Euroscore: 24.6%). The Mitraclip device was successfully implanted in 95.8% of patients, resulting in a reduction of two or more degrees of MR. Thirty day and 12-month mortality rates were estimated to be 2.3% and 18.9%, respectively. CONCLUSIONS: MitraClip appears to be a safe therapeutic option for patients with FMR who are considered to be at high surgical risk.

The predictive value of baseline pulmonary hypertension in early and long term cardiac and all-cause mortality after transcatheter aortic valve implantation for patients with severe aortic valve stenosis: A systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH). OBJECTIVE: To determine the association of PH with early and late cardiac and all-cause mortality after TAVI. METHODS: We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed. RESULTS: In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality). CONCLUSION: This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.

Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to identify the clinical impact and prognostic significance of AF on a large cohort of patients with HCM. METHODS: Echocardiographic and clinical correlates, risk factors for AF and thromboembolic stroke and the prognostic significance of AF were evaluated in 509 patients with an established diagnosis of HCM. RESULTS: A total of 119 patients (23.4%) were diagnosed with AF during the index evaluation visit. AF patients had a higher prevalence of stroke and presented with worse functional impairment. Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40). AF was an important risk factor for overall mortality (HR=3.4, 95% CI: 1.7-6.5), HCM-related mortality (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even after adjusting for statistically significant clinical and demographic risk factors. However, AF did not affect the risk for sudden death. CONCLUSIONS: LA size is an independent predictor of both AF and thromboembolic stroke. Moreover, patients with AF, regardless of type, have significantly higher mortality rates than patients without AF.

Determinants of functional mitral regurgitation severity in patients with ischemic cardiomyopathy versus nonischemic dilated cardiomyopathy.

AIMS: Functional mitral regurgitation (MR) is prevalent among patients with left ventricular (LV) dysfunction and is associated with a poorer prognosis. Our aim was to assess the primary determinants of MR severity in patients with ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Patients with functional MR secondary to ICM (n = 55) and DCM (n = 48) were prospectively enrolled. Effective regurgitant orifice (ERO) area, global LV remodeling, regional wall-motion abnormalities, and mitral apparatus deformity indices were assessed utilizing conventional and tissue Doppler echocardiography. ICM patients had more severe MR compared with DCM patients despite similar ejection fraction and functional status (ERO = 0.16 ± 0.08 cm(2) vs. ERO = 0.12 ± 0.70 cm(2) , respectively, P = 0.002). Regional myocardial systolic velocities in mid-inferior and mid-lateral wall were negatively correlated with ERO in ICM and DCM patients, respectively. Multivariate analysis identified coaptation height as the only independent determinant of ERO in both groups. In a subset of ICM patients (n = 9) with relatively high ERO despite low coaptation height, a higher prevalence of left bundle branch block was detected (88.9% vs. 46.7%, P = 0.02). CONCLUSIONS: Functional MR severity was chiefly determined by the extent of mitral apparatus deformity, and coaptation height can provide a rapid estimation of MR severity in heart failure patients. Additional contributory mechanisms in ICM patients include depressed myocardial systolic velocities in posteromedial papillary muscle attaching site and evidence of global LV dyssynchrony.

Patients with hypertrophic cardiomyopathy at risk for paroxysmal atrial fibrillation: advanced echocardiographic evaluation of the left atrium combined with non-invasive P-wave analysis.

AIMS: The maintenance of sinus rhythm is crucial for the functional capacity of patients with hypertrophic cardiomyopathy (HCM). Using a multimodality approach, we attempted to identify potential predictors of paroxysmal atrial fibrillation (PAF) in HCM patients. METHODS AND RESULTS: Thirty HCM patients (17 males, mean age 57.9 ± 13.6) with at least one documented PAF episode and 32 age- and sex-matched HCM control patients as well as 25 healthy volunteers were studied in sinus rhythm. Study subjects underwent 2D echocardiography including a colour Doppler myocardial imaging evaluation of the left atrium (LA). Additionally, an orthogonal electrocardiogram was acquired; P-wave duration, maximum, and mean energies were calculated for each subject at each orthogonal lead and the composite vector axis using the Morlet wavelet analysis. Compared with HCM controls, in HCM-PAF patients, LA antero-posterior diameter was significantly enlarged (LADAP: 46.1 ± 5.9 vs. 40.0 ± 4.7 mm, P < 0.001), peak strain rate of the LA lateral wall in the reservoir phase was significantly decreased (LAT peak SR-S: 1.93 ± 0.51 vs. 2.55 ± 0.83 s(-1), P < 0.01), and P-wave duration in the Z-lead was significantly prolonged (P-durZ: 106.9 ± 24.6 vs. 86.2 ± 14.3 ms, P < 0.001). Cut-off values and areas under the curve (AUCs) for individual parameters were 42.0 mm, 2.32 s(-1), and 98.8 ms and 0.81, 0.74, and 0.78, respectively. A multivariable model combining LADAP, LAT peak SR-S and P-durZ had an AUC of 0.90, a sensitivity of 0.87, and a specificity of 0.91 for identifying PAF patients. CONCLUSION: P-wave duration combined with LA antero-posterior diameter and myocardial deformation indices resulted in a higher power for discriminating HCM-PAF patients, when compared with individual parameters derived from either wavelet analysis or 2D echocardiography.

Beneficial effect of ischemic preconditioning on post-infarction left ventricular remodeling and global left ventricular function.

BACKGROUND: Preinfarction angina (PA) is a clinical analogue of ischemic preconditioning that improves postinfarct prognosis. Data concerning the association of PA with post infarction left ventricular (LV) remodeling and LV diastolic function are limited. We aimed to evaluate this association in patients with acute myocardial infarction (AMI) in the modern clinical era of widespread use of revascularization and antiremodeling medical treatment. METHODS: We studied 53 patients with anterior AMI who underwent complete reperfusion and received up to date antiremodeling medical treatment. LV remodeling, systolic and diastolic function were assessed using 2D echocardiography at baseline and 6 at months follow-up. Patients were divided into two groups regarding the presence or absence of PA. RESULTS: LV remodeling at follow-up was less frequent in the PA group (25 vs. 55 %, P<.05). Patients with PA had lower end-systolic volume index at baseline and follow up (24.1±6 vs. 30.1±14 ml/m(2), P<.001 and 25.3±8 vs. 35.6±2 ml/m(2), P=.001 respectively). Additionally at 6 months, they had better LV ejection fraction (52.1±9 vs. 42.9±10 %, P=.002) and exhibited improved diastolic filling as reflected by mitral E/e' (14.6±5 vs. 18.8±8, P=.05). CONCLUSIONS: Ischemic preconditioning in the form of PA promotes better LV systolic and diastolic function in the mid-term and is associated with less postinfarct LV remodeling in this specific study population. The results of the study underline the possible need for further risk stratification of AMI patients regarding the absence of PA.

The role of uric acid in stroke: the issue remains unresolved.

BACKGROUND: Although in the past decade a large number of studies have been performed to identify the relationship between uric acid and stroke, the issue remains unresolved and it is not clear whether the correlation between uric acid and stroke is circumstantial or causal. REVIEW SUMMARY: Some studies have found uric acid predictive for the development of cardiovascular disease, whereas others have failed to identify uric acid as a significant and independent risk factor after controlling for other atherosclerotic risk factors. Furthermore, uric acid, a powerful endogenous antioxidant, is increased in oxidative stress situations such as stroke. Still, it remains controversial whether elevated serum uric acid is neuroprotective or injurious at the onset of acute stroke. CONCLUSIONS: Large trials are required to provide definite answers in clinical practice and to reevaluate the goals of hypouricemic treatment in subjects with increased cardiovascular risk or during an acute cardiovascular event like stroke. This review tries to keep pace with the data concerning the association between uric acid and stroke.

Prognostic significance of right ventricular diastolic function in thalassaemia major.

While left ventricular (LV) restrictive filling pattern is an ominous echocardiographic finding in thalassaemia major (TM), the prognostic significance of right ventricular (RV) diastolic function in patients with TM has not been thoroughly investigated. We studied 45 TM asymptomatic transfusion-dependent patients with normal LV systolic function by Doppler echocardiography. The 15-year cumulative survival rate was 34% in patients with RV restrictive filling pattern (RFP) and 82% in patients with RV non-RFP (log-rank = 10.41, p = 0.0013). Doppler estimation of RV filling pattern is very important in evaluating the prognosis of TM patients and should be performed routinely and using a standardised followup protocol.

Aortic elastic properties are related to left ventricular diastolic function in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of the study was to evaluate left ventricular diastolic function and its relation to aortic wall stiffness in patients with type 1 diabetes mellitus without coronary artery disease or hypertension. PATIENTS: Sixty-six patients with type 1 diabetes mellitus were examined by echocardiography and divided into two groups according to the diastolic filling pattern determined by mitral annulus tissue Doppler velocities. Group A patients (n = 21) presented diastolic dysfunction with a peak early diastolic mitral annular velocity (Em)/peak late diastolic mitral annular velocity (Am) ratio <1 whereas in group B patients (n = 45) the Em/Am ratio was >1. Coronary artery disease was excluded based on normal thallium scintigraphy. Aortic stiffness index was calculated from aortic diameters measured by echocardiography, using accepted criteria. RESULTS: Aortic stiffness index differed significantly among the two groups. Significant correlations were found between parameters of left ventricular diastolic function (Em/Am, isovolumic relaxation time, deceleration time) and aortic stiffness index. Multiple stepwise linear regression analysis revealed aortic stiffness index (beta = -0.39, p = 0.001) and isovolumic relaxation time (beta = -0.46, p < 0.001) as the main predictors of Em/Am ratio. CONCLUSIONS: Aortic stiffness is increased in type 1 diabetic patients with left ventricular diastolic dysfunction. This impairment in aortic elastic properties seems to be related to parameters of diastolic function.

Impact of autonomic neuropathy on left ventricular function in normotensive type 1 diabetic patients: a tissue Doppler echocardiographic study.

Cardiovascular autonomic neuropathy (CAN) is one of the most serious complications of diabetes and has been weakly linked with left ventricular (LV) diastolic dysfunction. Previous studies that explored this association either suffer from inadequate definition of CAN or have mainly used conventional Doppler or nuclear techniques to investigate LV diastolic function. Tissue Doppler imaging (TDI) has evolved as a new quantitative tool for the assessment of cardiac systolic function, diastolic function, and the hemodynamics of LV filling. We sought to investigate conventional and TDI-derived indexes of LV systolic and diastolic function in type 1 diabetic patients with and without CAN and also in normal control subjects. Our findings suggest that the presence of CAN seems to have an additive effect on LV diastolic dysfunction in type 1 diabetes.

Utility of tissue Doppler imaging in predicting outcome in patients with idiopathic pulmonary fibrosis.

BACKGROUND: There are limited reports in the literature concerning right ventricular (RV) performance in patients with non end-stage idiopathic pulmonary fibrosis (IPF) who exhibit mild to moderate pulmonary hypertension (PH). We evaluated RV functional impairment in such a cohort using both conventional echocardiography and tissue Doppler imaging (TDI) and in addition we assessed the association of specific TDI indices with survival. METHODS: Twenty-two clinically stable patients with non-end stage IPF and mild to moderate PH were assessed. Twenty-two healthy individuals served as controls. We evaluated RV systolic and diastolic function and further estimated peak pulmonary artery systolic pressure (PASP). In addition, by combining TDI and Doppler echocardiography, we calculated the ratio of trans-tricuspid E-wave velocity to early diastolic tricuspid annulus velocity (RV E/Em). Patients were followed for a median period of 22 months and the incidence of death was recorded. RESULTS: Both echocardiographic modalities revealed impaired RV systolic and diastolic function in the IPF group compared to controls. A significant negative correlation was observed between RV E/Em and PASP (r = -0.5, p = 0.018). The probability of survival was 54.5% for those patients with RV E/Em < 4.7 versus 100% for those with an index > 4.7 (log-rank statistic 5.81, p = 0.016). CONCLUSIONS: TDI modality may serve as an alternative to conventional ultrasound technique for risk stratification and PH estimation in non end-stage IPF patients.

Clinical significance of tissue Doppler imaging in patients with hypertrophic cardiomyopathy.

BACKGROUND: A transmitral E/septal Ea ratio > or =15 is a predictor of adverse outcome in cardiac disease, so it was hypothesized that a septal E/Ea >/=15 would predict the risk of adverse outcome, including sustained ventricular tachycardia (VT), cardiac arrest, implantable cardioverter defibrillator (ICD) discharge, or sudden death (SD) in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: The study group comprised 96 consecutive patients with HCM (median age 53 years) who completed all noninvasive tests for risk stratification. The endpoint of the study was defined as death, cardiac arrest, documented sustained VT, or ICD-discharge. The median follow-up was 20.6 months. All patients were alive at the end of follow-up, although 8 patients had reached the endpoint during the study period. The variables that were predictive of adverse clinical outcome were family history of premature SD (p=0.03), syncope (p<0.001), maximum wall thickness > or =3 cm (p=0.02), and septal E/Ea > or =15 (p<0.001). In a stepwise multivariable model the only independent prognostic indicator was a septal E/Ea > or =15 (relative risk 0.26, 95% confidence interval 0.2-0.58, p<0.001). The cumulative event-free survival rate was 78.9% in patients with septal E/Ea > or =15, and 100% in patients with septal E/Ea <15 (p=0.0003). CONCLUSIONS: Septal E/Ea > or =15 predicts patients with HCM who are at risk of sustained VT, cardiac arrest, ICD-discharge, or SD. (Circ J 2007; 71: 897 - 903).

Early diastolic impairment of diabetic heart: the significance of right ventricle.

BACKGROUND: Left ventricular diastolic dysfunction represents the earliest preclinical manifestation of diabetic cardiomyopathy. Right ventricular function has not been studied in depth yet in diabetic patients, although the right ventricle has an important contribution to the overall cardiac function. This study was designed to assess diastolic and systolic ventricular function in both ventricles, in patients with type 1 diabetes, free from coronary artery disease and hypertension. METHODS: We studied 66 type 1 diabetic patients and 66 age- and sex-matched normal subjects by conventional and tissue Doppler echocardiography. A possible correlation was examined for age, diabetes duration and echocardiographic measurements of left ventricular and right ventricular functions with univariate analysis. RESULTS: Type 1 diabetic patients were found to have impaired diastolic function in both ventricles with either conventional or tissue Doppler echocardiography. On the contrary, systolic function in both ventricles was preserved in our diabetic population. The measured indexes showed an expected correlation with age and diabetes duration except from systolic velocity in tricuspid annulus determined by color tissue Doppler. Moreover, significant correlations were found among parameters of left and right ventricular function. CONCLUSIONS: Patients with type 1 diabetes mellitus have impaired diastolic function, and particularly relaxation, in both ventricles before the development of myocardial systolic dysfunction. These alterations in myocardial function may be attributed to ventricular interdependence as well as to the uniform effect of diabetes to cardiac function.

Improved papillary muscle function attenuates functional mitral regurgitation in patients with dilated cardiomyopathy after cardiac resynchronization therapy.

BACKGROUND: Functional mitral valve regurgitation attenuation after cardiac resynchronization therapy (CRT) in patients with severe heart failure has been attributed to both the increased rate of left ventricular systolic pressure increase and to papillary muscle (PM) recoordinated contraction. We hypothesized that an increase in systolic deformation of the PMs or the adjacent myocardial wall may in part account for this effect, by preventing their outward displacement during systole. METHODS: We studied by echocardiography 22 patients with moderate/severe functional mitral valve regurgitation and a mean ejection fraction of 18 +/- 4% at baseline and after implantation of a CRT system. RESULTS: CRT induced a significant reduction of the effective regurgitant orifice area (0.18 +/- 0.11 vs 0.35 +/- 0.17 mm2, P < .001). Strain improved in both PMs and their adjacent walls, although this improvement was significant only in anterolateral PM (-16 +/- 4.7 vs -11 +/- 4.3%, P = .02) and posteromedial PM adjacent wall (-16 +/- 10 vs -8 +/- 4.6%, P = .01). CONCLUSIONS: CRT acutely reduces the severity of functional mitral valve regurgitation in patients with heart failure and this effect may be in part attributed to improved strain of PM or adjacent wall.