Marina Verrengia

Abnormal regional myocardial deformation properties and increased aortic stiffness in normotensive patients with aortic coarctation despite successful correction: an ABPM, standard echocardiography and strain rate imaging study

The long-term follow-up data subsequent to a successful repair of AoC (aortic coarctation) show that life expectancy remains reduced. Previous standard echocardiographic studies have demonstrated normal or increased systolic cardiac function in patients following successful repair of AoC. SR (strain rate) imaging is a new technique able to detect subclinical myocardial abnormalities. In the present study we investigated whether young patients (without hypertension, as assessed using ambulatory blood pressure monitoring and an exercise test) following successful AoC repair already have abnormal myocardial deformation properties, and the relationship of the deformation properties with aortic stiffness. We studied 166 subjects, 83 AoC non-hypertensive patients (mean age 12+/-4 years) a number of years after successful repair of AoC and 83 age- and sex-matched subjects as controls. Peak systolic SR (1/s) for both regional longitudinal and radial function was assessed. The aortic stiffness index was calculated from the echocardiographically derived thoracic aortic diameters, and the measurement of blood pressure was obtained by cuff sphygmomanometry. The LV (left ventricular) ejection fraction was significantly increased in AoC patients, whereas regional longitudinal SRs were significantly reduced (-1.1+/-0.9 compared with -2+/-0.5, P<0.0001) in patients. The aortic stiffness index was significantly increased in AoC patients (12+/-9, P<0.0001). At multilinear regression analysis, age at repair (P=0.005; coefficient, -0.201; S.E.M., 0.027) and the aortic stiffness index (P=0.0029; coefficient, 0.334; S.E.M., 0.423) predicted longitudinal SR. Despite the presence of a successful repair for AoC, in the absence of hypertension, longitudinal deformation properties were significantly impaired. Moreover, the degree of longitudinal SR impairment was correlated with age at repair and aortic stiffness. Early repair can delay the onset of hypertension in postcoarctectomy patients, but cannot prevent the innate structural and functional abnormalities of the aorta and their deleterious effect on myocardial deformation properties.

Non Sustained Ventricular Tachycardia in Hypertrophic Cardiomyopathy and New Ultrasonic Derived Parameters

BACKGROUND The mechanism of sudden death in hypertrophic cardiomyopathy (HCM) is ventricular tachyarrhythmia emanating from myocyte disarray, fibrosis, and inhomogeneity in intramyocardial activation. Tissue synchronization imaging (TSI) allows the measurement of regional delay, while two-dimensional strain can be used to identify myocardial fibrosis. The aim of this study was to assess the relationship between new ultrasonically derived parameters and nonsustained ventricular tachycardia (NSVT) in patients with HCM. METHODS Ninety-three patients with HCM (mean age, 36 +/- 16 years) and 30 patients with hypertension with secondary left ventricular (LV) hypertrophy (mean age, 42 +/- 10 years; 65% men) were studied. All underwent standard echocardiographic, TSI, and two-dimensional strain examinations. Patients were followed every 3 months for 2 years. Holter monitoring was performed every 3 months. The primary endpoint was the occurrence of NSVT. RESULTS Twenty-four patients (26%) had >or=1 episode of NSVT. Patients with NSVT had a higher value of maximal LV thickness (22 +/- 6 vs 19 +/- 5 mm, P = .04). There were no significant associations between NSVT on Holter monitoring and LV outflow gradient, New York Heart Association class, syncope, and medical therapy. N-terminal pro-brain natriuretic peptide values were significantly (P = .01) higher in patients with NSTV (1034 +/- 1088 vs 561 +/- 593 pg/mL). Patients with HCM and NSVT had (1) similar values on TSI-studied parameters to patients without NSVT, (2) significant reductions in basal and mid septal strain and in basal anterior-septal strain, and (3) more frequently peak systolic strain >or= -10% (P < .0001). In multivariate analysis, the presence of >3 LV segments with longitudinal two-dimensional strain >or= -10% (sensitivity, 81%; specificity, 97.1%; area under the curve, 0.944; P < .0001) was an independent predictor of NSVT. CONCLUSIONS Using a simple, inexpensive, easily available, and bedside-usable tool, it was possible to recognize with good sensitivity and specificity patients with HCM at higher risk for NSVT.

Subclinical hypothyroidism and Down’s syndrome; studies on myocardial structure and function

Background: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged l-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by l-thyroxine therapy. As SH frequently affects children with Down’s syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. Aims: To establish whether SH influences myocardial structure and function in children with DS. Methods: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. Results: None of the 16 patients had myocardial impairment. Conclusion: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged l-thyroxine therapy is not clear cut.

Myocardial Ultrasound Tissue Characterization in Patients with Hypertrophic Cardiomyopathy: Noninvasive Evidence of Electrical and Textural Substrate for Ventricular Arrhythmias

BACKGROUND Although in patients with hypertrophic cardiomyopathy (HCM) pathologic studies seem to suggest a correlation between morphologic findings and arrhythmias, it has never been confirmed in the clinical setting. OBJECTIVE We sought to noninvasively assess the electrical and textural properties of the myocardium and to define their potential relationship in patients with HCM. METHODS We studied 48 patients: 22 with HCM (mean age: 22 +/- 5.1 years) and 26 age- and body surface area-matched healthy patients. They underwent a standard echocardiographic examination to assess left ventricular size and thickness. In addition, by integrated backscatter analysis, we assessed textural properties of left ventricular myocardium with calibrated averaged intensity (IB) and to assess functional properties of the myocardium with cyclic variation, both at the interventricular septum (IVS) and posterior wall. Finally, we studied ventricular late potentials (VLPs) by signal-averaged electrocardiography and performed a 24-hour electrocardiography Holter monitoring to respectively define electrical instability and ventricular arrhythmias. RESULTS Compared with control patients, patients with HCM had, both at IVS and posterior wall, increased IB (-28.8 +/- 10 vs -35 +/- 4 dB [P =.007] and -29 +/- 8 vs -33 +/- 5 dB [P <.035], respectively) and decreased cyclic variation (6.8 +/- 2.7 vs 10.3 +/- 2.3 dB [P <.001] and 8.2 +/- 2.9 vs 11.4 +/- 2.1 dB [P <.001], respectively). In all, 5 patients with HCM had positivity of VLPs, and 4 of them showed nonsustained ventricular tachycardia (nsVT) on the Holter monitoring. Compared with patients who had HCM without VLPs and nsVT, patients with positivity of VLPs and nsVT showed higher IB both at IVS (-15.8 +/- 8.4 vs -32.6 +/- 5.9 dB [P <.001] and -16.6 +/- 9.5 vs -31.5 +/- 7.5 dB [P =.002], respectively) and at posterior wall (-19.08 +/- 8.42 vs -32.5 +/- 4.2 dB [P <.001] and -22.4 +/- 4.6 vs -31 +/- 7.5 [P =.04], respectively). A multivariate analysis showed IB at IVS (P =.042; odds ratio = 1.19) and positivity of VLPs (P =.026; odds ratio = 3.67) as independent predictors of nsVT. CONCLUSION Patients with HCM showed abnormal morphologic and electrical properties of the myocardium. The correlation between VLPs and IB at IVS and their relationship with nsVT suggests a link between textural and electrical nonhomogeneity of myocardial fibers, a potential substrate of nsVT in patients with HCM.

Heart rate variability is a weak predictor of sudden death in children and young patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) carries a relatively high risk of sudden death, particularly in young people.1,2 To date, the clinical significance of heart rate variability (HRV) in patients with HCM is still controversial.3,4 Our study aimed to analyse HRV in a relatively large cohort of children and young patients with HCM, and to assess potential correlations with clinical markers of sudden death. In all, 53 patients diagnosed with HCM between the ages of 18 and 40 years and body surface area-matched controls were included in this study. The diagnosis of HCM was based on echocardiographic evidence of increased wall thickness, 2 standard deviations (SD) or more compared with age, sex and body surface area-matched people. Maximal ventricular wall thickness (MWT) was defined as the greatest thickness in any segment and measured as the absolute value and as Z score. At the time of the study, age of patients ranged from 1 to 220 months (mean 75.6 (SD 73.7)). Patients with HCM underwent physical examination, rest electrocardiography, conventional echocardiography, exercise test and 24-h …

Left ventricle myocardial mechanics and textural properties in patients with Williams syndrome.

Objective To study left ventricular mechanics and textural properties in patients with Williams syndrome to define the impact of left ventricular hypertrophy on the functional findings. Methods Echocardiography was performed in 16 Williams syndrome patients (aged 1–25 years, mean 10 ± 6 years), four with associated supravalvular aortic stenosis and seven with systemic hypertension. Fifteen age- and body surface area-matched subjects were selected as control group. Particularly, left ventricular geometry, myocardial contractility [midwall rate-corrected circumferential fiber shortening/end-systolic meridional wall stress relationship (σes)] and left ventricular diastolic function (mitral flow pattern and isovolumic relaxation time) were defined. In addition, integrated backscatter (IB) analysis intensity (IntIB) and cyclic variation (CVIB) were assessed for an ultrasonic myocardial characterization. Results Left ventricular hypertrophy was demonstrated in nine patients (56%) and abnormal left ventricular remodeling in ten patients (62%). Particularly seven of seven hypertensive patients and three of four patients with supravalvular aortic stenosis had abnormal remodeling; left ventricular geometry was normal in patients without hypertension or supravalvular aortic stenosis. In addition, midwall rate-corrected circumferential fiber shortening/(σes) relationship was within the normal range in all patients. At integrated backscatter analysis, Williams syndrome patients showed, both at interventricular septum and posterior wall, reduced CVIB (9.36 ± 2.16 versus 10.3 ± 1.3 and 8.65 ± 2 versus 10.5 ± 1.1). Compared to Williams syndrome patients without left ventricular hypertrophy (7/16), those with left ventricular hypertrophy (9/16) showed decreased mitral E/A ratio (1.32 ± 0.09 versus 1.62 ± 0.02), increased isovolumic relaxation time (68 ± 7 versus 53 ± 7) and increased IntIBS at interventricular septum (−27.3 ± 0.07 versus −34 ± 5). Conclusions Our data obtained in young Williams syndrome patients show that: (i) mild left ventricular functional and textural abnormalities may be detected also in absence of significant supravalvular aortic stenosis and/or hypertension; (ii) significant left ventricular hypertrophy may develop since childhood; (iii) differences in left ventricular remodeling and/or degree of left ventricular hypertrophy may occur. Further studies are required to define the real impact of the functional abnormalities on the natural history in patients with Williams syndrome.

Management of Arrhythmias in Heart Failure

Heart failure patients are predisposed to develop arrhythmias. Supraventricular arrhythmias can exacerbate the heart failure symptoms by decreasing the effective cardiac output and their control require pharmacological, electrical, or catheter-based intervention. In the setting of atrial flutter or atrial fibrillation, anticoagulation becomes paramount to prevent systemic or cerebral embolism. Patients with heart failure are also prone to develop ventricular arrhythmias that can present a challenge to the managing clinician. The management strategy depends on the type of arrhythmia, the underlying structural heart disease, the severity of heart failure, and the range from optimization of heart failure therapy to catheter ablation. Patients with heart failure, irrespective of ejection fraction are at high risk for developing sudden cardiac death, however risk stratification is a clinical challenge and requires a multiparametric evaluation for identification of patients who should undergo implantation of a cardioverter defibrillator. Finally, patients with heart failure can also develop symptomatic bradycardia, caused by sinus node dysfunction or atrio-ventricular block. The treatment of bradycardia in these patients with pacing is usually straightforward but needs some specific issue.

Diagnostic clues for the diagnosis of nonsarcomeric hypertrophic cardiomyopathy (Phenocopies): Amyloidosis, fabry disease, and mitochondrial disease

Hypertrophic cardiomyopathy (HCM) is the most common known inherited heart disorder, with a prevalence of 1:500 of the adult population. Etiology of HCM can be heterogeneous, with sarcomeric gene disease as the leading cause in up to 60% of the patients, and with a number of possible different diseases (phenocopies) in about 10%–15% of the patients. Early diagnosis of storage and infiltrative disorders, particularly those with specific treatments (i.e., Fabry disease and/or amyloidosis), means early management and treatment, with a significant impact on patients prognosis. Here, we report on four different cases of HCM, highlighting difficulties to make differential diagnosis of different forms of cardiomyopathies, and their potential impact on the management.

Exercise speckle-tracking strain imaging demonstrates impaired right ventricular contractile reserve in hypertrophic cardiomyopathy

AIMS To analyse right ventricular (RV) systolic function in patients with hypertrophic cardiomyopathy (HCM) at rest and during exercise, and its possible correlation with left ventricular(LV) morphology and function. METHODS AND RESULTS Standard echo, exercise stress echo, and RV 2D speckle-tracking strain (2DSE) were performed in 45 patients with HCM and in 45 age- and sex-comparable healthy controls. RV global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. LV mass index and IVS wall thickness were significantly increased in HCM, while LV ejection fraction, RV diameters, RV tissue Doppler systolic peak and the RV end-systolic pressure-area relationship at rest were comparable between the two groups. Conversely, all transmitral Doppler indexes were significantly impaired in HCM. In addition, RV GLS and regional peak myocardial RV strains were significantly reduced in patients with HCM (all P<0.001). During physical effort, LV ejection fraction was comparable between the two groups. Conversely, LV E/Em ratio was significantly increased in HCM. Increase in TAPSE and RV tissue Doppler Sm peak velocity during effort were similar between the two groups. Conversely, increases of RV end-systolic pressure-area, regional and global RV strain were significantly lower in HCM patients (RV lateral strain: 10.3±3.5% of increase in HCM vs 20.5±4.5% in controls; p<0.0001). Multivariable analysis detected independent associations of RV lateral strain at peak stress with LV IVS thickness, maximal workload during exercise, and LV E/Em ratio during effort (all p<0.0001). An RV lateral 2DSE cut-off point of -14% differentiated controls and HCM with an 86%sensitivity and a 92% specificity. CONCLUSIONS RV contractile reserve for HCM is impaired and this suggests that the lower resting values of RV in HCM may represent early subclinical myocardial damage, closely associated with exercise capacity.

560 Quantification of left ventricular function in patients with hypertrophic cardiomyopathy: an ultrasound based regional strain and strain rate imaging study

Background: The echocardiographic evaluation of myocardial systolic function in pts with hypertrophic cardiomyopathy (HCM) is still unsatisfactory. This disease has been shown to exhibit LV relaxation and filling abnormalities despite normal LV ejection fraction (EF). However, EF only detects radial motion and the normal value of systolic function described in HCM pts may be due to a relative insensitivity of the used technique. Strain (S) and Strain Rate (SR) imaging is a new technique able to quantify both radial and longitudinal regional myocardial deformations and potentially is more sensitive compared to 2D grey scale imaging. Methods: We studied 25 HCM pts (aged 16±3 yrs) using standard grey scale echocardiography and S/SR imaging. Regional peak systolic longitudinal function was assessed from the apical views while regional peak systolic radial function was evaluated from the parasternal views. We studied also the time to peak systolic deformation (from the onset of ECG Q wave to the peak systolic S) for both radial and longitudinal function, in the mid segment of posterior wall from the apical 3 chamber view and the parasternal view, respectively. Data were compared with that of 33 age comparable healthy subjects. Results: All pts showed a normal LVEF. Radial peak systolic S and SR in HCM pts were comparable to healthy subjects. Conversely, regional longitudinal function was significantly reduced when compared to healthy subjects (S [%]: HCM=10±6 vs healthy subjects =25±5, p<0.01; SR[1/s]: HCM = -1.2±0.6 vs healthy subjects = -1.8±0.3, p<0.01). This reduction was also found in? apparently? nonhypertrophied segments. In HCM pts the time to both radial and longitudinal systolic peaks were significantly prolonged when compared to healthy subjects. Moreover, while in healthy subjects the time to longitudinal systolic peak (290±37ms) was shorter than the time to radial systolic peak (310±37 ms), in HCM pts the time to longitudinal systolic peak (388±56 ms) was longer than the radial one (344±28 ms). Conclusions: Despite a normal LVEF, systolic longitudinal deformation is significantly reduced in HCM pts and this reduction is present also in the? apparently? normal segments. S/SR imaging demonstrated in HCM that longitudinal function not only is reduced but is also delayed in this disease.