The growing role of echocardiography in interventional cardiology: The present and the future.

As structural heart disease interventions continue to evolve to a sophisticated level, accurate and reliable imaging is required for pre-procedural selection of cases, intra-procedural guidance, post-procedural evaluation, and long-term follow-up of patients. Traditionally, cardiovascular procedures in the catheterization laboratory are guided by fluoroscopy and angiography. Advances in echocardiography can overcome most limitations of conventional imaging modalities and provide successful completion of each step of any catheter-based treatment. Echocardiography's unique characteristics rendered it the ideal technique for percutaneous catheter-based procedures. The purpose of this review is to demonstrate the use of the most common and up-to-date echocardiographic techniques in recent non-coronary percutaneous interventional procedures, underlining its inevitable and growing role, as well as illustrating areas of weakness and limitations, and to provide future perspectives.

Comparative microRNA profiling in relation to urinary albumin excretion in newly diagnosed hypertensive patients.

Microalbuminuria is an established early marker of endothelial dysfunction and damage. MicroRNAs (miRNAs) are emerging as essential modulators of cardiovascular physiology and disease. In the present study, we sought an association between the differential expression of related miRNAs in the peripheral blood mononuclear cells of untreated patients with newly diagnosed essential hypertension and the levels of urinary albumin excretion. We assessed the expression of the miRNAs miRNA-1, miRNA-133a, miRNA-26b, miRNA-208b, miRNA-499 and miRNA-21 in consecutive subjects with untreated newly diagnosed essential hypertension (aged 62.5±9.7 years) and with no indications of other organic heart disease. MiRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription-polymerase chain reaction. The prevalence of microalbuminuria was 9.8%. miRNA-208b and miRNA-133a were independently correlated with 24-h urinary albumin excretion. More specifically, a strong association was found between the gene expression levels of miRNA-208b in our patients' peripheral blood cells and urinary albumin (r=0.72, P<0.001). A similar association was found for miRNA-133a (r=0.372, P<0.001). In conclusion, miRNA-208b and miRNA-133a show distinct profiling in peripheral blood cells isolated from untreated patients with recently diagnosed essential hypertension. Their gene expression levels reveal a strong correlation with urinary albumin excretion levels. Our findings provide new perspectives on the development of a new generation of biomarkers for the better monitoring of end-organ damage in hypertension.

Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process.

Differential expression of vascular smooth muscle-modulating microRNAs in human peripheral blood mononuclear cells: novel targets in essential hypertension.

Vascular smooth muscle cell (VSMC) phenotypic plasticity has a critical role in the pathophysiology of arterial remodeling in essential hypertension. MicroRNAs are emerging as potential biomarkers and therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-143, miR-145, miR-21, miR-133 and miR-1, which are implicated in VSMC phenotypic modulation, in 60 patients with essential hypertension and 29 healthy individuals. All patients underwent 24-h ambulatory blood pressure (BP) monitoring. MicroRNA levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed lower miR-143 (2.20±0.25 versus 4.19±0.57, P<0.001), miR-145 (13.51±1.73 versus 22.38±3.31, P=0.010) and miR-133 (8.15±1.32 versus 37.03±8.18, P<0.001) and higher miR-21 (3.08±0.32 versus 2.06±0.31, P=0.048) and miR-1 (33.94±5.19 versus 12.35±2.13 P=0.006) expression levels compared with controls. In hypertensive patients, we observed correlations of miR-143 (r = -0.380, P=0.003), miR-145 (r=-0.405, P=0.001), miR-21 (r=-0.486, P<0.001) and miR-133 (r=0.479, P<0.001) expression levels with 24-h diastolic BP. Furthermore, we observed correlations of miR-21 (r=-0.291, P=0.024), miR-1 (r=-0.312, P=0.015) and miR-133 (r=0.310, P=0.016) levels with the dipping status. Associations of miR-143 (r=-0.292, P=0.025), miR-145 (r=-0.399, P=0.002), miR-21 (r=-0.343, P=0.008) and miR-133 (r=0.370, P=0.004) levels with 24-h mean pulse pressure were also found. Our data provide important evidence that VSMC-modulating microRNAs are closely related to essential hypertension in humans and they may represent potential therapeutic targets in essential hypertension.

Myocardin gene regulatory variants as surrogate markers of cardiac hypertrophy - study in a genetically homogeneous population.

Myocardin is thought to contribute to heart hypertrophy as assessed in animal models. The aim of this study was to identify polymorphisms on the myocardin gene and investigate possible relationships with left ventricular structure in human hypertrophic cardiomyopathy (HCM). Eighty-four native Cretan individuals (36 patients with HCM and 48 healthy controls) were examined by direct sequencing and subsequent restriction fragment length polymorphism analysis and six polymorphisms were identified in the promoter region at positions -435T>C (rs758187), -629A>T (rs8071072), -1030C>G (rs1233851), -1069A>G, -1166A>G and -1406G>A (rs976906). Allele and haplotype frequencies were not significantly different between patients and controls. However, patients carrying the [-435C;-629T] allelic variant had decreased left ventricular wall thickness (LVWT, p = 0.020) and left ventricular mass (p = 0.006) as compared with the wild-type genotype. Carrier status of this myocardin promoter allelic variant was also associated with significant lower myocardin mRNA levels in peripheral blood (p = 0.039). Thus, a myocardin promoter allelic variant existing in the normal Cretan population was associated with decreased left ventricular mass in HCM patients and decreased myocardin mRNA levels in peripheral blood. Our results may be limited by the limited sample size, but are strengthened by the genetic homogeneity of the Cretan population. Our data suggest that functional natural myocardin promoter variation might be a genetic factor contributing to inter-individual differences in the development of cardiac hypertrophy.

Impedance cardiography derived cardiac output in hemodialysis patients: a study of reproducibility and comparison with echocardiography.

BACKGROUND: Hemodialysis patients experience a variety of hemodynamic abnormalities that contribute to cardiovascular disease mortality which is the leading cause of death in these patients. Impedance cardiography has been utilized in order to monitor cardiac hemodynamics with lower cost and inconvenience, but it has not been appropriately validated in the hemodialysis population. AIM: We repeatedly used impedance cardiography to assess short- (48 hours) and long-term (15 days) reproducibility of cardiac output measurements and we compared baseline impedance cardiography measurements with echocardiographic measurements. PATIENTS AND METHODS: We studied 109 stable hemodialysis patients, aged 59.70 +/- 11.97 years being on hemodialysis for 67.59 +/- 40.15 months, on a non-dialysis day. Cardiac output was obtained with the BioZ impedance cardiography system (Cardiodynamics, San Diego, Ca, USA). Baseline echocardiography was performed using a Hewlett-Packard Sonos 2500 (Andover, Mass., USA). RESULTS: The values of impedance cardiography derived cardiac output were 5.28 +/- 0.79, 5.27 +/- 0.75 and 5.25 +/- 0.74 l/min at baseline (107 patients), 48 hours (107 patients) and 15 days (98 patients) respectively, showing high reproducibility. Bland and Altman analysis estimated that bias at 48 hours and at 15 days were: -0.013 (95% confidence intervals = -0.045 to 0.019) and 0.028, (95% confidence intervals = -0.044 to 0.101), respectively. In addition baseline impedance cardiography derived cardiac output was significantly correlated with the echocardiographic derived cardiac output (r = 0.9, p < 0.0001). CONCLUSION: Impedance cardiography is a simple non invasive technique for cardiac output estimation in hemodialysis patients which has high reproducibility when performed under controlled conditions, and is closely correlated with echocardiographic measurements of cardiac output.

Alteration of proximal aorta biophysical properties in patients with end stage renal disease.

OBJECTIVE: To present a novel, non-invasive echocardiographic application to assess the structural and functional properties of the complex composition of the proximal aorta in patients with end stage renal disease (ESRD). METHODS: 71 haemodialysis patients (mean (SD) age 61.3 (9.3) years, dialysis duration 79.2 (51.6) months) and 62 age matched controls were studied. From the suprasternal view, the distance between ascending and descending aorta was measured with two dimensional ultrasound. The aortic flow wave transit time was measured with pulsed wave Doppler. M mode echocardiography, with simultaneous blood pressure estimates, was used to assess the diameters of the aortic annulus and of the ascending aorta. Pulse pressure, pulse wave velocity (PWV), pressure strain elastic modulus, characteristic impedance, and beta index were calculated. RESULTS: Patients had increased pulse pressure (68.0 (7.2) v 51.4 (5.0) mm Hg, p < 0.001), PWV (6.1 (1.1) v 3.9 (0.6) m/s, p < 0.001), characteristic impedance (174 (58) v 111 (31) m/s.cm2, p < 0.001), pressure strain elastic modulus (872 (254) v 541 (140) mm Hg, p < 0.001), and beta index (8.9 (3.4) v 5.5 (1.4), p < 0.001) compared with controls. In patients PWV was correlated with age and time on haemodialysis (r = 0.44, p < 0.001, and r = 0.51, p < 0.001, respectively). CONCLUSION: A novel application of duplex ultrasound of the proximal aorta showed that patients with ESRD have impaired proximal aortic function compared with controls. The data indicate that these non-invasive measurements can be used to describe status and change in aortic biophysical properties and may be used as a marker for cardiovascular disease risk.

Segmental pattern of myocardial sympathetic denervation in idiopathic dilated cardiomyopathy: relationship to regional wall motion and myocardial perfusion abnormalities.

BACKGROUND: Iodine 123-labeled metaiodobenzylguanidine (MIBG) has been used to study cardiac adrenergic nerve activity. Cardiac MIBG uptake is diminished in patients with heart failure. However, it is not known how this reduction is related to regional abnormalities of myocardial wall motion or perfusion. METHODS AND RESULTS: We studied 24 patients with idiopathic dilated cardiomyopathy (ejection fraction <45%) and 15 healthy control subjects using I-123 MIBG cardiac imaging, echocardiographic assessment of wall motion abnormalities, technetium 99m sestamibi perfusion scintigraphy, and hemodynamic assessment. Cardiac MIBG was significantly correlated with ejection fraction (r = 0.67), cardiac index (r = 0.57), left ventricular wall motion score index (r = -0.68), and systolic wall stress (r = -0.61). MIBG was lower in patients than in control subjects (1.43 +/- 0.19 vs 2.05 +/- 0.02; P <.01), whereas the washout rate was higher (P <.01). Moreover, a significant correlation was found between the reduction in MIBG uptake and the severity of echocardiographic wall motion abnormalities in the anterior wall (r = 0.543), apex (r = 0.530), and septum (r = 0.675), as well as with the severity of decrease in resting myocardial perfusion in the anterior wall (r = 0.480) and septum (r = 0.580). CONCLUSIONS: Patients with idiopathic dilated cardiomyopathy show not only global but also regional abnormalities of cardiac sympathetic innervation. The severity of these changes is partially correlated with abnormalities of regional wall motion and myocardial perfusion.

QT dispersion in patients with mitral valve prolapse is related to the echocardiographic degree of the prolapse and mitral leaflet thickness.

BACKGROUND: Ventricular arrhythmias are common in patients with mitral valve prolapse (MVP). Previous studies have provided evidence that a higher degree of systolic mitral valve displacement and the presence of a thickened anterior mitral leaflet are related to an increased incidence of complex ventricular arrhythmias and risk of sudden death in these patients. The aim of our study was to investigate whether QT dispersion in patients with MVP is associated with the echocardiographic degree of the prolapse and mitral leaflet thickness. METHODS: QT and JT intervals and dispersions were measured in 89 patients with primary mitral valve prolapse (26 men and 63 women with mean age 39 +/- 14 years). All patients underwent a full echocardiographic examination and a scoring system was used to determine the degree of MVP. Anterior mitral leaflet thickness was also measured. Twenty-four hour Holter monitoring was used to assess ventricular arrhythmogenesis. RESULTS: According to their echocardiographic score. patients were divided into three groups (Group A. B and C) reflecting the different degrees of the prolapse. QT dispersion in patients with the highest degree of MVP, i.e. Group C was significantly greater (65 +/- 13 ms) than that of the other two groups (Group A: 38 +/- 14 ms, P<0.005 and Group B: 45 +/- 12 ms, P<0.005). Similar differences between groups were also found for JT dispersion. Multiple regression analysis revealed that among the demographic and clinical variables that were tested, only the echocardiographic degree of the prolapse and anterior mitral leaflet thickness were independently associated with QT dispersion. Holter monitoring showed that the incidence of complex ventricular arrhythmias was also higher in patients with more severe MVP. CONCLUSIONS: Our results indicate that QT and JT dispersions are related to the echocardiographic degree of MVP and mitral leaflet thickness. The echocardiographic assessment of the severity of the prolapse may help to identify a subgroup of patients at increased risk of life-threatening arrhythmias.

Aortic atherosclerotic lesions in the thoracic aorta detected by multiplane transesophageal echocardiography as a predictor of coronary artery disease in elderly patients.

BACKGROUND: The presence of atherosclerotic lesions in the thoracic aorta by transesophageal echocardiography (TEE) appears to be a marker for the presence of significant coronary artery disease (CAD) in the general population. HYPOTHESIS: We investigated whether atherosclerotic lesions in the thoracic aorta, by multiplane TEE, could be a marker for CAD in elderly patients. METHODS: In all, 127 patients (67 men, 60 women, aged 68 +/- 13 years), underwent a TEE study with imaging of the thoracic aorta and cardiac catheterization with coronary angiography. The presence of a distinct, linear, or focal, highly echogenic mass protruding into the vessel lumen was the criterion for the diagnosis of atherosclerotic plaque. RESULTS: Atherosclerotic lesions were found in 30 of 36 patients (83.3%) with and in 20 of 91 (22%) without CAD. Of the 41 patients > or = 70 years, atherosclerotic lesions were detected in 14 of 17 (82.3%) with and in 13 of 24 patients (54%) without CAD. The sensitivity, specificity, and positive and negative predictive values in this group were 82.3, 46, 52, and 78.6%, respectively. Multivariate logistic regression analysis revealed that in patients aged > or = 70 years only advanced atherosclerotic lesions were independent predictors of significant CAD. However, the high negative predictive value of the method indicates that the absence of aortic plaque is a strong predictor of the absence of CAD. CONCLUSIONS: The presence of atherosclerotic lesions in the thoracic aorta is a strong predictor of CAD only in patients < 70 years old. However, the negative predictive value of the method is high for all patients regardless of age.

Relation of autonomic modulation to recurrence of atrial fibrillation following cardioversion.

The aim of this study was to investigate the time course of changes in autonomic nervous system activity in patients with long-standing atrial fibrillation (AF) following internal electrical conversion to sinus rhythm and to look for differences between patients who do and do not relapse. Time-domain indexes of heart rate variability were calculated from 24-hour Holter recordings on the day of conversion and 1 day and 1 month afterward for 22 patients with chronic (> 3 months) AF. Ten healthy subjects served as a control group. During the day of cardioversion the mean RR interval and its circadian variation differed significantly between controls and patients. The mean values of successive RR intervals that deviated by > 50% from the prior RR interval and the root-mean-square of successive RR interval differences--indexes of vagal modulation--were initially significantly higher in patients than in controls but showed a decrease (p < 0.05) by the second day (from 12.4 +/- 7% to 8.1 +/- 5% to 7.3 +/- 5% and from 49 +/- 9 to 39 +/- 12 to 41 +/- 11 ms, respectively) to levels similar to those of the controls (7.6 +/- 5% and 40 +/- 17 ms, respectively). Only these 2 indexes contained significant prognostic information about relapse: patients who later relapsed had higher initial values than those who did not, and these values remained high during the 2 days after conversion. In conclusion, this study provides data confirming that spontaneous chronic AF in humans results in a significant increase in vagal tone that is reversed with time after restoration of sinus rhythm. Persistently higher values of vagal tone are observed in patients who relapse, and are probably a predictor for recurrence.

Left ventricular diastolic filling pattern predicts cardiopulmonary determinants of functional capacity in patients with congestive heart failure.

BACKGROUND: Abnormalities of diastolic function are an important determinant of exercise intolerance in patients with heart failure. However, the relation between left ventricular filling pattern and cardiopulmonary exercise performance has not been adequately studied. METHODS: Thirty-one patients with idiopathic (n = 14) or ischemic (n = 17) dilated cardiomyopathy, demonstrated by coronary angiography, and radionuclide ejection fraction 30.5% +/- 9% underwent cardiopulmonary exercise testing with a modified Naughton protocol and a complete echocardiographic study. Patients were subdivided into restrictive and nonrestrictive groups according to their Doppler transmitral flow pattern. Gas exchange data were measured during exercise testing. The relation of left ventricular filling pattern to cardiopulmonary parameters was assessed in both groups. RESULTS: Exercise duration was similar in the restrictive and nonrestrictive groups but significant differences were found in oxygen consumption (VO(2)) at peak exercise (14.3 +/- 2.4 vs 20.4 +/- 4.7 mL/kg per minute; P <.001) and at the anaerobic threshold (VO(2AT)) (13 +/- 2.2 vs 17.3 +/- 3 mL/kg per minute; P <.001). Simple linear regression analysis revealed that both peak VO(2) and VO(2AT) were significantly correlated with the ratio of peak early (E wave) to late (A wave) transmitral filling velocity, early filling deceleration time, atrial filling fraction, and A-wave velocity but not with left ventricular ejection fraction. Multivariate regression analysis gave only the peak A-wave velocity as an independent predictor for both peak VO(2) and VO(2AT). CONCLUSIONS: In patients with heart failure, abnormalities of diastolic function are the most important determinant of exercise intolerance. A restrictive transmitral flow pattern by Doppler echocardiography is a marker of diminished cardiopulmonary exercise performance in these patients.

Dobutamine- vs exercise-induced ST segment elevation early after Q wave myocardial infarction. Prediction of functional recovery after revascularization.

AIMS: The association between stress-induced ST elevation and functional recovery following revascularization after myocardial infarction remains unclear. We assessed the relative accuracy of dobutamine- and exercise-induced ST elevation in Q wave leads in predicting functional recovery following revascularization, and we investigated the relationship of ST elevation to different wall motion responses to dobutamine. METHODS AND RESULTS: Thirty-nine patients underwent dobutamine stress echo and exercise test 8+/-2 days after Q wave myocardial infarction. All patients underwent angiography and subsequent revascularization. Follow-up echocardiograms were obtained 7+/-4 weeks after revascularization. Functional recovery was assessed by the difference between the baseline and the follow-up asynergy index. Nineteen patients (48%) developed dobutamine- and exercise-induced ST elevation. There was significant agreement between the tests (k=0.58, P<0.001). We found a significant correlation between dobutamine and exercise-induced ST elevation with functional recovery following revascularization (r=0. 45, P<0.005 and r=0.7, P<0.001, respectively). The parameters with the highest predictive value for functional recovery were: (a) the biphasic response during dobutamine infusion, (b) the development of ST elevation in both tests, and (c) the development of exercise-induced ST elevation in more than three leads. CONCLUSION: There is a strong association between dobutamine- and exercise-induced ST elevation with functional recovery following revascularization. Exercise-induced ST elevation in more than three leads and a biphasic response during dobutamine infusion accurately predict functional recovery.

Autonomic nervous system activity before and during episodes of myocardial ischemia in patients with stable coronary artery disease during daily life.

Spectral analysis of heart rate variability (HRV) was used to assess changes in the autonomic nervous system (ANS) 10 minutes before, during, and 10 minutes after 110 ischemic episodes (IEs) in 38 patients (25 men, age 61 +/- 10 years) with stable coronary artery disease. In 26 of 77 diurnal IEs (07:00-22:59) there were no changes in the spectral indexes (LF and HF) during the study period. In the remainder there was an increase in the LF:HF ratio due to HF withdrawal that started before the onset of the IE. All 33 nocturnal episodes also showed an increase in the LF:HF ratio, which was due not only to HF withdrawal, but also to a simultaneous increase in LF. Although it is not the only cause, the ANS plays a significant role in triggering IEs during daily life in patients with stable coronary artery disease. The common factor in all such episodes is a gradual withdrawal of parasympathetic tone.