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.

Asymptomatic versus symptomatic episodes in patients with paroxysmal atrial fibrillation via long-term monitoring with implantable loop recorders.

BACKGROUND: The presentation of atrial fibrillation (AF) varies remarkably, from totally asymptomatic to symptomatic patients, while the same individual may present symptomatic and asymptomatic episodes. We aimed to identify electrocardiographic differences between symptomatic and asymptomatic episodes and to find parameters related to the appearance of symptoms. METHODS: Thirty consecutive patients (age 66.9±10years) with paroxysmal AF received an implantable loop recorder. Three types of episodes were defined: asymptomatic (ASx), symptomatic (Sx), and mixed asymptomatic-symptomatic (AS-Sx). The heart rate (HR) and heart rate variability (HRV) were recorded during the first 2min of each ASx or Sx episode, and during the first 2min of both the symptomatic and asymptomatic periods in AS-Sx. RESULTS: Eighty-two episodes from twenty-five patients were evaluated. Mean HR was 142.48±25.84bpm for Sx and 95.71±19.29bpm for ASx (p<0.001). Mean HRV was 92.62±42.29ms for Sx and 150.06±49.68ms for ASx (p<0.001). In AS-Sx, mean HR was 102.91±24.54bpm for the asymptomatic and 141.88±23.43bpm for the symptomatic period (p<0.001). Mean HRV was 173.55±61.30ms for the asymptomatic and 87.33±30.65ms for the symptomatic period (p=0.003). There were no significant correlations between patients' characteristics and the clinical presentation of the arrhythmia. CONCLUSIONS: The ASx were characterized by a lower HR and higher HRV compared to Sx. In As-Sx, the asymptomatic period was characterized by a lower HR and higher HRV compared to the symptomatic. These findings suggest a possible contribution of variations in the autonomic nervous system activity to the perception of the arrhythmia.

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 gene expression of bradykinin receptors 1 and 2 in peripheral monocytes from patients with essential hypertension.

Bradykinin participates in various hypertensive processes, exerted via its type 1 and type 2 receptors (BKR1 and BKR2). The aim of the study was to investigate BKR1 and BK2R gene expression in peripheral monocytes in patients with essential hypertension compared with healthy individuals. Seventeen hypertensive patients (9 males, age 56 ± 7 years) and 12 healthy individuals (7 males, age 55 ± 6) participated. Mononuclear cells isolated using anti-CD14+ antibodies and mRNAs of BKR1 and BKR2 were estimated by real-time quantitative reverse transcription-PCR. Both BKR1 and BKR2 showed significantly upregulated gene expression in the group of hypertensive patients. Specifically, BKR1 gene expression was 142.1 ± 42.2 in hypertensives versus 20.2 ± 8 in controls (P = 0.024) and BKR2 was 1222.2 ± 361.6 in hypertensives versus 259.5 ± 99.1 in controls (P = 0.038). Antihypertensive treatment resulted in a decrease in BKR1 (from 142.1 ± 42.2 to 55.2 ± 17.1, P = 0.065) and in BKR2 (from 1222.2 ± 361.6 to 256.8 ± 81.8, P = 0.014) gene expression. BKR1 and BKR2 gene expression on peripheral monocytes is upregulated in essential hypertension. This may lead to functional changes in monocytes and contribute to the development of target organ damage in hypertensive patients.

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.

Arterial stiffness in hypertensives in relation to expression of angiopoietin-1 and 2 genes in peripheral monocytes.

Angiopoietins (Angs) are important angiogenic and endothelial cell growth factors with many functions, including influence on the vascular wall. Pulse-wave velocity (pwv) is an independent marker of cardiovascular adverse outcome in hypertensives, although all the pathophysiological mechanisms that affect it have not yet been determined. We investigated the relationship between arterial stiffness and Ang-1 and Ang-2 gene expression in the peripheral blood monocytes of hypertensive patients. We studied 53 patients who had untreated grade-1 or grade-2 essential hypertension and no indications of other organic heart disease. Carotid-femoral (c-f) and carotid-radial (c-r) artery waveforms were measured and pwv was determined. The monocytes were isolated using anti-CD14(+) antibodies and mRNAs were estimated by real-time quantitative reverse transcription-PCR. Ang-1 gene expression was strongly correlated with both c-f-pwv (r=0.952, P<0.001) and c-r-pwv (r=0.898, P<0.001). Similarly, Ang-2 gene expression was significantly correlated with both c-f-pwv (r=0.471, P=0.002) and c-r-pwv (r=0.437, P=0.003). Our data provide important evidence that Ang-1 and Ang-2 gene expression levels in peripheral monocytes are closely related with pwv in patients with essential hypertension. This positive correlation may suggest a link between angiogenesis and arterial stiffness in those patients.

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.

The role of the post-cardioversion time course of hs-CRP levels in clarifying the relationship between inflammation and persistence of atrial fibrillation.

OBJECTIVES: Although recent studies suggest that inflammation is involved in the pathogenesis of atrial fibrillation (AF), it remains controversial whether it is a consequence or a cause of the arrhythmia. DESIGN: Prospective study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: In 52 patients with persistent AF lasting >3 months, high-sensitivity C-reactive protein (hs-CRP) was measured before and after electrical cardioversion. MEASUREMENTS AND RESULTS: All patients were successfully cardioverted to sinus rhythm (SR), but the recurrence rate was 23% at 1 month. Baseline hs-CRP was higher in patients with AF recurrence than in those who remained in SR (0.5 (SD 0.18) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001). Similarly, arrhythmia recurrence was associated with greater left atrial diameters (45.4 (SD 3.3) mm vs 40.7 (SD 3.1) mm, respectively, p<0.001). However, logistic regression analysis showed that hs-CRP was the only independent predictor for AF recurrence (p<0.001). Additionally, patients who were in SR on final evaluation had significantly lower hs-CRP levels than at baseline (0.10 (SD 0.06) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001), while those who experienced AF recurrence had similar values on final and on initial evaluation (0.56 (SD 0.24) mg/dl vs 0.50 (SD 0.18) mg/dl, respectively, p = 0.42). CONCLUSION: High levels of hs-CRP are associated with an increased risk of AF recurrence after cardioversion. The restoration and maintenance of SR result in a gradual decrease of hs-CRP while AF recurrence has a different effect, suggesting that inflammation is a consequence, rather than a cause, of AF.

Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

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.