The Fundamental Role of Stress Echo in Evaluating Coronary Artery Disease in Specific Patient Populations.

Stress echocardiography (SE) was initially used for assessing patients with known or suspected coronary heart disease by detecting and evaluating myocardial ischemia and viability. The implementation of SE has gradually been extended to several cardiovascular diseases beyond coronary artery disease, and SE protocols have been modified and adapted for the detection of coronary artery disease (CAD) or other cardiovascular diseases in specific patient populations. This review attempts to summarize current data concerning SE implementation and clinical value in these specific and diverse populations: patients with an intramural course of a coronary artery, known as a myocardial bridge, chronic severe or end-stage hepatic disease, chronic severe or end-stage kidney disease, cardiac allograft vasculopathy, patients scheduled for solid-organ transplantation and other intermediate and high-risk surgery and, finally, patients treated with anticancer drugs or radiotherapy.

Cardiac Masses: The Role of Cardiovascular Imaging in the Differential Diagnosis.

Cardiac masses are space occupying lesions within the cardiac cavities or adjacent to the pericardium. They include frequently diagnosed clinical entities such as clots and vegetations, common benign tumors such as myxomas and papillary fibroelastomas and uncommon benign or malignant primary or metastatic tumors. Given their diversity, there are no guidelines or consensus statements regarding the best diagnostic or therapeutic approach. In the past, diagnosis used to be made by the histological specimens after surgery or during the post-mortem examination. Nevertheless, evolution and increased availability of cardiovascular imaging modalities has enabled better characterization of the masses and the surrounding tissue. Transthoracic echocardiography using contrast agents can evaluate the location, the morphology and the perfusion of the mass as well as its hemodynamic effect. Transesophageal echocardiography has increased spatial and temporal resolution; hence it is superior in depicting small highly mobile masses. Cardiac magnetic resonance and cardiac computed tomography are complementary providing tissue characterization. The scope of this review is to present the role of cardiovascular imaging in the differential diagnosis of cardiac masses and to propose a step-wise diagnostic algorithm, taking into account the epidemiology and clinical presentation of the cardiac masses, as well as the availability and the incremental value of each imaging modality.

The Tree of Sirtuins and the Garden of Cardiovascular Youth.

Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which participate in numerous molecular pathways involved in various age-related human diseases, such as type II diabetes, cardiovascular (CV) diseases and cancer. They have a major role in apoptosis, inflammation, oxidative stress and metabolism regulation, traits that have a great impact on CV physiology and pathology. Their unique profile of NAD+ energy dependency makes them an appealing target for human intervention in cellular and metabolic processes. This review focuses on the recent advances of SIRTs research aiming to shed light on the emerging roles of SIRTs in the pathophysiology of CV and metabolic diseases.

Epigenetics, the missing link in hypertension.

Epigenetics refers to functional alterations in gene expression or phenotype without any change of the underlying DNA sequence. It is the study of the potential of a cell or organism to express different traits through functional regulation of its gene transcription. Though it is met as a necessary process in biology, epigenetics may often play a crucial part in the development of specific pathologic conditions, including cardiovascular diseases and hypertension.

Correlation of arm position and exercise test interpretation.

ST-segment changes during exercise testing can be attributed mainly to ischemia, but also, in some patients, to other physiological parameters, such as body position or hyperventilation, making ECG exercise test interpretation more complex. Here we describe the case of a patient who had an electrocardiographically positive exercise test, in order to illustrate the correlation between arm position and ST changes during exercise testing.

Diastolic myocardial dysfunction does not affect survival in patients with cirrhosis.

Left ventricular diastolic dysfunction (DDF) has been considered as a component of cirrhotic cardiomyopathy. The clinical significance of DDF in cirrhotics has not been clarified. We prospectively evaluated the echocardiographic-Doppler, tissue-Doppler (TDI) findings of left ventricular function and survival in cirrhotics with or without DDF. Seventy-six cirrhotics without endogenous heart disease were included. DDF was diagnosed by mitral inflow Doppler parameters and diastolic myocardial velocities. Assessments of demographics, liver dysfunction, laboratory, echocardiographic systolic/diastolic indices, TDI of mitral annular motion and M-mode echocardiography were recorded. Patients were followed-up for a median of 25 months (15-40). DDF was diagnosed in 51 (67%) patients. Patients with compared with those without DDF had significantly older age and higher pulse rate as well as more frequently severe ascites, greater aortic root diameter and interventricular septal thickness. There was no difference in systolic myocardial function between two groups. Patients with DDF had a trend for worse survival (long rank, P = 0.094). A multivariate analysis showed that age, MELD and sodium but no DDF were predictive of death. DDF is prevalent in advanced cirrhosis and is associated with severe ascites. Systolic myocardial function and mortality do not seem to be strongly affected by the presence of DDF.

Tricuspid regurgitation after successful mitral valve surgery.

The tricuspid valve (TV) is inseparably connected with the mitral valve (MV) in terms of function. Any pathophysiological condition concerning the MV is potentially a threat for the normal function of the TV as well. One of the most challenging cases is functional tricuspid regurgitation (TR) after surgical MV correction. In the past, TR was considered to progressively revert with time after left-sided valve restoration. Nevertheless, more recent studies showed that TR could develop and evolve postoperatively over time, as well as being closely associated with a poorer prognosis in terms of morbidity and mortality. Pressure and volume overload are usually the underlying pathophysiological mechanisms; structural alterations, like tricuspid annulus dilatation, increased leaflet tethering and right ventricular remodelling are almost always present when regurgitation develops. The most important risk factors associated with a higher probability of late TR development involve the elderly, female gender, larger left atrial size, atrial fibrillation, right chamber dilatation, higher pulmonary artery systolic pressures, longer times from the onset of MV disease to surgery, history of rheumatic heart disease, ischaemic heart disease and prosthetic valve malfunction. The time of TR manifestation can be up to 10 years or more after an MV surgery. Echocardiography, including the novel 3D Echo techniques, is crucial in the early diagnosis and prognosis of future TV disease development. Appropriate surgical technique and timing still need to be clarified.

Left ventricle enlargement and increased systolic velocity in the mitral valve are indirect markers of the hepatopulmonary syndrome.

BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) has been associated with left atrial enlargement, but the presence of other markers of left and right diastolic and/or systolic cardiac dysfunction has not been clarified. We prospectively evaluated the possible associations between echocardiographical-Doppler findings and HPS. METHODS: Seventy-nine cirrhotic patients without endogenous heart or pulmonary disease were included. HPS was diagnosed by the presence of increased arterial-alveolar-difference and intrapulmonary right-to-left shunt at contrast-enhanced transthoracic echocardiography. Echocardiographical systolic and diastolic indices, tissue Doppler imaging (TDI) of mitral and tricuspid annular motion and M-mode echocardiography measurements were recorded. RESULTS: Hepatopulmonary syndrome was diagnosed in 12 (15.2%) patients. Patients with compared with those without HPS had significantly younger age, albumin levels and saturation of oxygen (SaO(2)) in an erect position, but higher left ventricular end diastolic diameter (LVEDD), ejection fraction, E-wave peak velocity of tricuspid valve, left atrial volume, TDI E wave (early diastolic period) at the right free wall/tricuspid annulus (cm/s) and TDI S wave (systolic) at the left lateral wall/mitral annulus (TDI Smv). In multivariate analysis, the presence of HPS was found to be independently associated with younger age (P=0.027), lower SaO(2) in an erect position (P=0.023), higher LVEDD (P=0.019) and higher TDI Smv (P=0.026). LVEDD and TDI Smv offered good diagnostic accuracy for HPS diagnosis (AUROC/c-statistic: 0.724 and 0.736 respectively). CONCLUSIONS: We confirmed that in patients with cirrhosis, the development of HPS is associated with higher cardiac output and hyperdynamic circulation. Left ventricle enlargement and higher systolic velocity in the mitral valve represent satisfactory indirect markers of HPS.

Clinical determinants of electrocardiographic and spatial vectorcardiographic descriptors of ventricular repolarization in healthy children.

BACKGROUND: Although the association of repolarization alterations to the development of life-threatening ventricular arrhythmias has received considerable research attention, there is paucity of data regarding what may be considered as normal, especially in children. METHODS: To define electrocardiographic (ECG) and vectorcardiographic (VCG) descriptors of ventricular repolarization in healthy school-age children, 12-lead digital ECGs were obtained from 646 children (348 males/298 females, mean age 8.54 ± 1.86 years). All QT intervals were measured manually using the digitally stored ECGs. Orthogonal X, Y, and Z leads were reconstructed from the standard 12-lead ECGs and the maximal amplitudes of the spatial QRS and T vectors were calculated, as well as the spatial QRS-T angle. RESULTS: The mean heart rate was 95.3 ± 15.8 bpm and the QRS duration was 83.4 ± 9.3 ms. Mean QT interval was 334.1 ± 24.2 ms and the corrected QT interval was 436.5 ± 23.8 ms (Bazzet) and 404.3 ± 19.4 ms (Fridericia). Although the uncorrected maximum and mean QT intervals were significantly higher in boys (P values 0.011 and 0.009, respectively), there was no difference in the rate-corrected QT interval. The spatial QRS and T-vector amplitudes were 1512.0 ± 365.7 µV and 478.8 ± 149.3 µV, respectively. The spatial QRS-T angle was 14.1 ± 8.0 degrees. Although the mean QT interval showed significant increase with age (P = 0.014), all VCG parameters did not show significant variance with age. CONCLUSIONS: A range of ECG and VCG descriptors of ventricular repolarization was determined in a large sample of healthy school-age children to provide a data basis of normal values for future reference.

The significance of right-sided chest leads in exercise testing for the detection of right ventricular dysfunction post myocardial infarction of the inferior wall.

BACKGROUND: The incorporation of right-sided chest leads (V(3)R-V(5)R) into the standard exercise testing has been reported to improve its diagnostic accuracy. The purpose of this study was to evaluate the ability of exercise testing in detecting right ventricular (RV) dysfunction post myocardial infarction (MI) of the inferior wall, using additional V(3)R-V(5)R leads. METHODS: We studied 133 patients (59 ± 5 years, 81 males) with a history of inferior MI due to right coronary artery obstruction (affirmed with coronary angiography). All patients underwent an echocardiographic assessment of RV function 4 weeks after discharge and an exercise treadmill test in order to detect possible RV dysfunction. Recordings during exercise were obtained with the standard 12 leads plus V(3)R-V(5)R. RESULTS: From 133 patients, 97 (group A) presented with normal right ventricle according to the echocardiographic study while the rest 36 patients (group B) presented with RV dysfunction. Maximal exercise-induced ST-segment deviation (in mm) was similar in the standard 12 leads for the 2 groups (2.1 ± 0.4 vs 1.8 ± 0.3, p = NS) while in V(3)R-V(5)R it was greater in group B (0.7 ± 0.3 vs 1.4 ± 0.4, p<0.05). Sensitivity, positive prognostic value, negative prognostic value and accuracy of exercise testing in detecting RV dysfunction were all improved using V(3)R-V(5)R (78 vs 47%, 39 vs 29%, 87 vs 75%, 62 vs 55% respectively, p<0.05 for all) while specificity was not deteriorated (56 vs 58%, p = NS). CONCLUSIONS: The addition of right-sided chest leads (V(3)R-V(5)R) improves the diagnostic ability of standard exercise testing in detecting and especially in excluding RV dysfunction post inferior MI.

Novel methodology for the detection of exercise-induced myocardial wall motion abnormalities by surface electrocardiogram during exercise test.

BACKGROUND: We investigated whether ischemia-induced wall motion abnormalities during exercise test modify electrical vector variation. METHODS: We performed treadmill exercise test and thallium 201 scintigraphy in 150 normotensives. Beat-to-beat change of direction of S wave in V(1) (reference lead) was compared with that of R wave in V(5) and aVF, representative of anterior and inferior walls, respectively. The percentage of neighboring QRS couples where S wave in V(1) and R wave in V(5) or aVF change toward the same direction (increase or decrease) constitutes V1-V5 and V1-aVF indexes. RESULTS: V1-V5 and V1-aVF indexes were significantly decreased in subjects with reversible anterior or inferior ischemia, respectively. A decrease in V1-V5 index ≥0.14 defines those with anterior wall ischemia (sensitivity, 100%; specificity, 75.5%), whereas a decrease in V1-aVF index ≥0.05 defines those with inferior wall ischemia (sensitivity, 92.3%; specificity, 61.5%). CONCLUSIONS: These novel electrocardiographic exercise test indexes improved significantly their sensitivities.

The impact of novel exercise criteria and indices for the diagnostic and prognostic ability of exercise testing.

Exercise testing (ET) stands as one of the most easy, affordable, cost effective, non invasive methods for diagnosing coronary heart disease. Its sensitivity, specificity and prognostic value, especially in the prime era of its implementation in the cardiac diagnostic procedure, is relatively limited. Novel exercise criteria and indices based either on ST segment changes or ST segment independent parameters, such as "Athens QRS score", have greatly improved the diagnostic ability and accuracy of ET. Complex ECG-derived indices linked to ST changes along with the use of right-sided precordial leads have also enhanced the diagnostic accuracy of ET with respect to the extent of ischemic heart disease and the detection of specific culprit vessels. ET contains also a prognostic value, since several ET-derived parameters have been associated with adverse outcome, including ST changes, blood pressure and heart rate response to exercise and duration of exercise.

Prevalence of interatrial block in healthy school-aged children: definition by P-wave duration or morphological analysis.

BACKGROUND: P waves > or = 110 ms in adults and > or = 90 ms in children are considered abnormal, signifying interatrial block, particularly in the first case. METHODS: To evaluate the prevalence of interatrial block in healthy school-aged children, we obtained 12-lead digital ECGs (Cardioperfect 1.1, CardioControl NV, Delft, The Netherlands) of 664 healthy children (349 males/315 females, age range 6-14 years old). P-wave analysis indices [mean, maximum and minimum (in the 12 leads) P-wave duration, P-wave dispersion, P-wave morphology in the derived orthogonal (X, Y, Z) leads, as well the amplitude of the maximum spatial P-wave vector] were calculated in all study participants. RESULTS: P-wave descriptor values were: mean P-wave duration 84.9 + or - 9.5 ms, maximum P-wave duration 99.0 + or - 9.8 ms, P dispersion 32.2 + or - 12.5 ms, spatial P amplitude 182.7 + or - 69.0 microV. P-wave morphology distribution in the orthogonal leads were: Type I 478 (72.0%), Type II 178 (26.8%), Type III 1 (0.2%), indeterminate 7 (1%). Maximum P-wave duration was positively correlated to age (P < 0.001) and did not differ between sexes (P = 0.339). Using the 90-ms value as cutoff for P-wave duration, 502 (75.6%) children would be classified as having maximum P-wave duration above reference range. The 95th and the 99th percentiles were in the overall population 117 ms and 125 ms, respectively. P-wave morphology type was not in any way correlated to P-wave duration (P = 0.715). CONCLUSIONS: Abnormal P-wave morphology signifying the presence of interatrial block is very rare in a healthy pediatric population, while widened P waves are quite common, although currently classified as abnormal.

Right-sided chest leads in exercise testing for detection of coronary restenosis.

BACKGROUND: The incorporation of right-sided chest leads (V(3)R through V(5)R) into standard exercise testing has been reported to improve its diagnostic utility. HYPOTHESIS: The purpose of this study was to evaluate any improvement in the ability of exercise testing in detecting restenosis, using additional V(3)R through V(5)R leads, in asymptomatic patients undergoing percutaneous coronary intervention (PCI) in the right coronary artery (RCA) or/and left circumflex (LCX). METHODS: We studied 172 consecutive patients (54 +/- 7 years old, 106 males) undergoing PCI in RCA or/and LCX. A treadmill test had been performed before PCI. Six months later, all patients underwent a second treadmill test and arteriography in order to detect silent ischemia due to restenosis. Recordings during exercise were obtained with the standard 12-leads plus V(3)R through V(5)R. RESULTS: Out of 172 patients, 106 had stenosis in RCA, 35 in LCX, and 31 in both vessels while 6 months later, restenosis was detected in 8 (for RCA), 3 (for LCX), and 3 (for both vessels) patients respectively. Sensitivity, specificity, positive prognostic value, negative prognostic value, and accuracy of exercise testing performed post PCI were ameliorated using V(3)R through V(5)R (79% vs 57%, 97% vs 80%, 69% vs 21%, 98% vs 95%, and 95% vs 78% respectively, P < .05 for all except negative prognostic value). Maximal exercise-induced ST-segment deviation (in mm) was not changed post PCI in 12 leads (1.4 +/- 0.2 vs 1.5 +/- 0.2, P = NS) while it was decreased in V(3)R through V(5)R (0.2 +/- 0.2 vs 1.2 +/- 0.3, P < .01). CONCLUSIONS: The addition of V(3)R through V(5)R improves the diagnostic ability of standard exercise testing in detecting silent ischemia due to restenosis in patients undergoing PCI in RCA or/and LCX.

Correlation of ST-segment "hump sign" during exercise testing with impaired diastolic function of the left ventricle.

BACKGROUND: The appearance of a discrete upward deflection of the ST segment, termed the ST hump sign during exercise testing has been associated with resting hypertension and exaggerated blood pressure response to exercise. OBJECTIVE: We investigated the correlation between the presence of hump sign during exercise testing with coexisting impaired diastolic function of the left ventricle (LV) at these patients. METHODS: We formed a cohort of 237 nonconsecutive patients (140 males, 41 +/- 5 years old) having undergone a treadmill test, according to the Bruce protocol, which divided into 2 groups: group A, including 130 patients which presented ST-segment hump sign at any of the leads of the electrocardiograms recorded during exercise, and group B, including 107 patients that didn't. All patients subsequently underwent an echocardiographic estimation of the LV diastolic function, using conventional and Tissue Doppler Imaging techniques. RESULTS: From 237 patients included in our study, 106 had echocardiographic signs of diastolic LV dysfunction. Among them, the appearance of ST hump sign at the peak of exercise testing was observed in 93 patients (88%), particularly in the inferior and lateral leads, while no ST hump sign was observed only in 13 patients (12%) with impaired diastolic LV function. CONCLUSIONS: The appearance of ST segment hump sign during exercise testing is strongly correlated with diastolic LV dysfunction and can be used as an exercise electrocardiographic index of diastolic LV dysfunction, independently from the echocardiographic study.

Effect of biventricular pacing on ventricular repolarization and functional indices in patients with heart failure: lack of association with arrhythmic events.

AIMS: We prospectively assessed the effects of biventricular (BiV) pacing on electrocardiographic (ECG) and vectorcardiographic (VCG) descriptors of ventricular depolarization and repolarization and their association with appropriate implantable cardioverter defibrillator (ICD) activation. METHODS AND RESULTS: We studied 70 consecutive heart failure (HF) (37 ischaemic) patients (64 males, age 66.3 years) with a history of syncope or sustained ventricular tachycardia (VT) who underwent implantation of a BiV-ICD. An invasive electrophysiological study (EPS) was performed before the implantation and 12-lead digital ECGs before and 30 days after implantation. Serial echocardiographic studies were performed. Follow-up duration was 1 year. Maximum (P < 0.001) and minimum (P = 0.004) QT intervals were significantly decreased, whereas QT dispersion was not altered (P = 0.086). QRS duration was shortened (P < 0.001), whereas QRS dispersion was significantly decreased (P = 0.034). Spatial T and QRS vector amplitudes decreased (P < 0.001, for both), whereas the spatial QRS-T angle was not affected (P = 0.671). Twenty-seven (38.6%) patients, experienced appropriate ICD therapies during follow-up. None of the ECG or VCG parameters (pre- or post-implant) were able to identify patients with appropriate ICD therapies during follow-up. Only the presence of a previous episode of sustained VT (spontaneous or inducible on EPS) was strongly associated with appropriate ICD therapies (multivariate P = 0.00 014; odds ratio 24.5). CONCLUSION: Improvement or no alteration of ECG and VCG descriptors of ventricular depolarization and repolarization was demonstrated after implantation of a BiV-ICD in HF patients. None of these parameters were associated with appropriate ICD therapies, whereas a previous episode of VT or induction of sustained VT on EPS predicted appropriate ICD treatments.

Electrocardiographic criteria for detecting coronary artery disease in hypertensive patients with ST-segment changes during exercise testing.

PURPOSE: It is well known that patients with arterial hypertension frequently present with ischemic electrocardiographic changes during exercise testing without actually having coronary artery disease (CAD). The purpose of this study was to establish additional electrocardiographic criteria during exercise testing for detecting CAD in hypertensive patients with ischemic ST-segment response. METHODS: Three hundred eighty-two consecutive hypertensive patients (224 males, 58 +/- 8 years) who presented with ischemic electrocardiographic changes during exercise testing and agreed to undergo coronary arteriography were included in the study. RESULTS: From 382 hypertensive patients undergoing coronary angiography, only 76 (20%) had significant coronary stenosis, whereas 306 (80%) had normal coronary arteries. From 382 patients, 287 (75%) (group A) presented with ST-segment depression during exercise in leads II-III-aVF-V(6), 271 (94%) of which had normal arteries at the angiography. The remaining 95 patients (25%) (group B) of the studied patients presented with ST-segment depression in II-III-aVF and/or V(4) through V(6), 60 (63%) of which had CAD. Furthermore, 251 patients of group A presented with ST-segment depression during the fourth to sixth minute of the recovery period in V(4) through V(6), 247 (98%) of which had normal arteries. Another 28 patients from group B presented with ST-segment depression during the fourth to eighth minute of the recovery period in V(4) through V(6), 22 (79%) of which had significant coronary artery stenosis. CONCLUSIONS: Hypertensive patients who present with ST-segment depression during exercise in leads II-III-aVF and/or V(4) through V(6) and with a prolonged duration of this depression at the recovery phase (fourth to eighth minute) are more likely to have CAD. Absence of ST-segment depression in V(4) and V(5) at the end of exercise or during the seventh and eighth minute of recovery favors a false-positive result.

A case of pseudomembranous colitis presenting with massive ascites.

Clostridium difficile-associated disease seems to be increasing worldwide. A wide spectrum of clinical manifestations, ranging from asymptomatic to life-threatening disease, has been described. A case of pseudomembranous colitis with massive ascites as the main presenting manifestation is described in order to illustrate the changing clinical pattern of antibiotic-associated colitis.