Biomedical subjects
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In patients with severe aortic valve stenosis (valve area 41.8 ml/min/1.73 m(2) (event-free survival rate of 38% vs 93%, p = 0.004). Thus, in patients with severe AS, comorbidities are frequent, and particularly kidney disease significantly impacts longterm outcome.
BACKGROUND: In patients with chronic heart failure (CHF), chronic kidney disease (CKD) is associated with increased morbidity and mortality, but contributing mechanisms are not well defined. This study tested the impact of CKD on intracardiac conduction, diastolic function and prognosis in patients with underlying CHF. METHODS: We prospectively enrolled 269 patients with stable CHF, of whom 135 had CKD (estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m(2)). Echo measurements comprised left ventricular dimensions/volumes, ejection fraction, mitral E/A-ratio, deceleration time and tissue Doppler mitral annular velocities (S', E', A'). PQ and QRS intervals were derived from the 12-lead ECG. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point. RESULTS: Patients with CKD had longer PQ and QRS intervals, and were in a poorer NYHA functional class as compared to patients without CKD. In patients with CKD, the mitral annular E' velocity was lower, the mitral E/E'-ratio was higher and a restrictive mitral filling pattern was more frequent. By linear regression analysis, PQ and QRS intervals and the mitral E/E'-ratio were inversely related to the eGFR. During a follow-up of 507+/-375 days, 39 patients suffered a cardiac event. In CKD patients, outcome was markedly poorer as compared to those without CKD (event-free survival rate 51% vs. 87% in those without KD, p=0.001) CONCLUSIONS: In patients with CHF, CKD is associated with impaired intracardiac conduction and progressive diastolic dysfunction. Both mechanisms may contribute to increased morbidity and mortality of such patients.
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinical data suggest that competitive sports may provoke ARVC in susceptible persons. Genetically, loss-of-function mutations in desmosomal proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with ARVC. To test the hypothesis that reduced desmosomal protein expression causes ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in mice. METHODS AND RESULTS: Ten-month-old heterozygous plakoglobin-deficient mice (plakoglobin+/-) had increased right ventricular volume, reduced right ventricular function, and spontaneous ventricular ectopy (all P<0.05). Left ventricular size and function were not altered. Isolated, perfused plakoglobin+/- hearts had spontaneous ventricular tachycardia of right ventricular origin and prolonged right ventricular conduction times compared with wild-type hearts. Endurance training accelerated the development of right ventricular dysfunction and arrhythmias in plakoglobin+/- mice. Histology and electron microscopy did not identify right ventricular abnormalities in affected animals. CONCLUSIONS: Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype is accelerated by endurance training. This suggests a functional role for plakoglobin and training in the development of ARVC.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor-site mutation in intron 5 (c.631-2A-->G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and the creation of a downstream premature termination codon. Quantitative analysis of cardiac DSC2 expression in patient specimens revealed a marked reduction in the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electron-dense midlines, and associated myocardial contractility defects. These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function.
This study compares quantitative and qualitative information on global and regional left ventricular (LV) function obtained with multidetector-row computed tomography (MDCT) with that obtained with magnetic resonance imaging (MRI) in patients with a high prevalence of LV wall motion abnormalities. Thirty patients (19 male, 63.7+/-15.1 years) with myocardial infarction (n=12), coronary artery disease (n=9), arrhythmogenic right ventricular cardiomyopathy (n=6), and dilation cardiomyopathy (n=3) were included. Segmental LV wall motion (LV-WM) was assessed using a 4-point scale. Wall thickness measurements were calculated in diastolic and systolic short axis images. Two hundred and fifty-two out of 266 (94.7%) normal and 189 out of 214 (88.3%) segments with decreased wall motion were correctly identified by MDCT, yielding a sensitivity of 88% and specificity of 95% for identification of wall motion abnormalities. LV-WM scores were identical in 86.7% of 480 segments (kappa=0.809). MDCT had a tendency to underestimate the degree of wall motion impairment. Interobserver agreement was lower in MDCT (66.5%) than in MRI (89.1%; p<0.01). Normokinetic segments are reliably identified with MDCT. Sensitivity for detection and accurate classification of LV wall motion abnormalities need to be improved. Better temporal resolution of the CT system seems to be the most important factor for enhancing MDCT performance.
BACKGROUND: In patients with chronic heart failure (CHF), N-terminal pro-brain natriuretic peptide (NT-proBNP) provides relevant prognostic information, but its usefulness in the presence of kidney disease has been questioned. METHODS: We prospectively enrolled 142 patients with stable CHF and a wide spectrum of renal function (estimated glomerular filtration rates [eGFRs] ranging from 17.1 to 100.3 ml/min/1.73 m2). Chronic kidney disease, defined as eGFR < 60 ml/min/1.73 m2, was present in 63 patients (44%). NT-proBNP measurements were carried out on a bench-top analyzer (Elecsys 2010). Cardiac death or urgent cardiac transplantation were considered as a combined study end-point. RESULTS: During a follow-up of 383 +/- 237 days, 19 patients underwent a cardiac event (cardiac death, n = 17; urgent cardiac transplantation, n = 2). By multivariate Cox analysis, including clinical and laboratory variables, NT-proBNP and serum hemoglobin were independent prognostic predictors. In patients with NT-proBNP > 1,129 pg/ml, outcome was significantly worse compared to patients with NT-proBNP < 1,129 pg/ml (event-free survival rate 67% vs 94% in those with NT-proBNP < 1,129 pg/ml, p = 0.001). By linear regression analysis, NT-proBNP levels were related to New York Heart Association (NYHA) functional class (R = 0.41, p < 0.001), and inversely related to eGFR (R = -0.29, p = 0.001) and to left ventricular ejection fraction (R = -0.43, p < 0.001). CONCLUSIONS: In CHF patients with and without kidney disease, NT-proBNP provides independent prognostic information. In such patients, NT-proBNP levels are not only reflective of a reduced clearance (i.e., a lower eGFR) but also of the severity of the underlying structural heart disease.
PURPOSE: Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by (123)I-meta-iodo-benzylguanidine scintigraphy ((123)I-MIBG SPECT), on the long-term prognosis of patients with IVF. METHODS: (123)I-MIBG SPECT was performed in 20 patients (mean age 37+/-13 years) with IVF. Mean follow-up of patients after study entry was 7.2+/-1.5 years (range 4.9-10.5 years). Ten patients (five men, five women; mean age 43+/-12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. RESULTS: Abnormal (123)I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal (123)I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal (123)I-MIBG uptake. CONCLUSION: Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of (123)I-MIBG SPECT during the long-term follow-up of these patients.
In patients with chronic heart failure and reduced systolic function, an implantable cardioverter-defibrillator (ICD) improves the prognosis, but morbidity and mortality remain high. We attempted to identify the prognostic impact of Doppler echocardiography and QRS duration in such patients. We prospectively enrolled 84 patients with chronic heart failure, an ICD, and impaired systolic function (mean ejection fraction 29 +/- 10%). Echocardiographic measurements included left ventricular dimensions/volumes, ejection fraction, mitral E/A ratio, deceleration time, and tissue Doppler analysis of mitral annular velocities (S', E', A'). A cardiac event (death from pump failure or appropriate ICD therapy, i.e., antitachycardia pacing/shock due to sustained ventricular tachycardia or ventricular fibrillation) was defined as the study end point. During a follow-up of 373 +/- 254 days, 22 patients (26%) had an event (death from pump failure, n = 7; patients who received an appropriate ICD therapy, n = 16). In patients with an event, the QRS duration was longer (169 +/- 41 vs 146 +/- 37 ms, p = 0.023), the mitral E/E' ratio was higher (16.0 +/- 6.5 vs 12.8 +/- 5.9, p = 0.044), and a restrictive filling pattern was more frequent (44% vs 9%, p = 0.017). Stepwise multivariate Cox regression analysis identified a restrictive filling pattern as the only independent predictor of an event (hazard ratio 3.65, 95% confidence interval 1.54 to 8.64, p = 0.003). For patients with a restrictive filling pattern, the outcome was markedly poorer than that for patients with a nonrestrictive pattern (event-free survival rate 38% vs 72%, p = 0.005). In conclusion, in patients with chronic heart failure, an ICD, and systolic dysfunction, a restrictive filling pattern is an independent predictor of adverse cardiac events.
BACKGROUND: For patients with chronic heart failure (CHF), left bundle branch block (LBBB) is associated with impaired systolic function and increased morbidity and mortality, but data on diastolic function are scarce. In this patient population, we attempted to define the impact of LBBB on diastolic function, filling pressures, and brain natriuretic peptide and its circulating N-terminal precursor (NT-proBNP) levels. METHODS: A total of 94 patients with stable CHF (48 with complete LBBB, 46 without intraventricular conduction delay and normal QRS duration) underwent conventional 2-dimensional/Doppler echocardiography and Doppler tissue analysis of mitral annular velocities. As a measure of left ventricular filling pressures, the ratio of peak early mitral flow velocity to peak early diastolic mitral annular velocity was derived. NT-proBNP measurements were carried out on a bench-top analyzer (Elecsys-2010, Roche Diagnostics, Mannheim, Germany). RESULTS: Patients with or without LBBB did not differ with respect to the cause of CHF or ejection fraction, but in LBBB deceleration time was shorter (163 +/- 66 vs 205 +/- 95 milliseconds, P = .021) and a restrictive mitral filling pattern was more frequent (35% vs 11%, P = .005). In such patients, the ratio of peak early mitral flow velocity to peak early diastolic mitral annular velocity was higher (14.5 +/- 6.2 vs 10.6 +/- 5.2, P < .001) and NT-proBNP was elevated (3553 +/- 3725 vs 850 +/- 896 pg/mL, P < .01) as compared with patients without LBBB. CONCLUSION: For patients with CHF and comparable systolic performance, LBBB is associated with more severe diastolic dysfunction, elevated filling pressures, and higher NT-proBNP levels. These findings may contribute to increased morbidity and mortality of such patients.
BACKGROUND: It was the aim of this study to compare the prognostic impact of echocardiography and brain natriuretic peptide and its N-terminal fragment (NT-proBNP) in patients with chronic heart failure (CHF). METHODS: In all, 73 patients with CHF underwent conventional 2-dimensional/Doppler echocardiography and Doppler tissue analysis of systolic, early and late diastolic mitral annular velocities. The mitral filling pattern was classified as restrictive or nonrestrictive. NT-proBNP measurements were carried out on a bench-top analyzer. A cardiac event (rehospitalization caused by worsening CHF, cardiac death, urgent cardiac transplantation) was defined as combined study end point. RESULTS: During follow-up of 226 +/- 169 days, 27 patients had an event (rehospitalization because of CHF, n = 18; cardiac death, n = 7; urgent transplantation, n = 2). On multivariate Cox regression analysis, a restrictive filling pattern, NT-proBNP, the ratio of peak early diastolic mitral flow to mitral annular E' velocity were independent prognostic predictors. A risk stratification model based on the 3 strongest independent predictors separated groups into those with good, intermediate, and poor outcome (event-free survival of 78%, 46%, and 0%, respectively). CONCLUSIONS: In patients with CHF, Doppler echocardiography, Doppler tissue imaging, and NT-proBNP provide independent and incremental prognostic information. A combined use of echocardiography and NT-proBNP may help to improve risk stratification in this patient population.
AIMS: We report three young patients presenting with life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) and/or survived sudden cardiac arrest, who were admitted to our institution for further diagnostic evaluation. METHODS AND RESULTS: In all patients, idiopathic left ventricular (LV) aneurysms were identified after a detailed non-invasive and invasive evaluation. Sustained VT/VF was inducible during programmed ventricular stimulation in two of the three patients. Left ventricular aneurysms were depicted and characterized by various imaging modalities (echocardiography, magnetic resonance imaging, LV angiography). To elucidate the pathogenesis further, both myocardial viability and regional sympathetic innervation were assessed by radionuclide imaging techniques. Defects of innervation and metabolism were documented in the area of the aneurysm but distal to the aneurysm there were no signs of downstream denervation. CONCLUSION: Life-threatening arrhythmias may be the first manifestation of an idiopathic LV aneurysm, which can be reliably diagnosed with modern imaging techniques. Radionuclide imaging may yield additional information as to the involvement of the autonomic nervous system potentially associated with arrhythmogenesis. Management strategies in patients with an idiopathic LV aneurysm range from antiarrhythmic drug treatment, implantation of an automatic cardioverter-defibrillator to surgical aneurysmectomy.
OBJECTIVE: Determination of left ventricular (LV) volumes and global function parameters from MDCT data sets is usually based on short-axis reformations from primarily reconstructed axial images, which prolong postprocessing time. The aim of this study was to evaluate the feasibility of LV volumetry and global LV function assessment from axial images in comparison with short-axis image reformations. SUBJECTS AND METHODS: This study consisted of 20 patients with either coronary artery disease or dilated cardiomyopathy. We evaluated MDCT results using cine MRI as the reference technique. RESULTS: LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were significantly overestimated by the axial MDCT approach in comparison with volume measurements from short-axis CT image reformations. The mean LV ejection fraction (LVEF) was not significantly different (41.2% vs 42.7%). Short-axis and axial MDCT determination of LVEF revealed a systematic underestimation by a mean +/- SD of -2.1% +/- 3.6% versus -3.6% +/- 8.2%, respectively, when compared with LVEF values based on cine MRI. The interobserver variability for volume and function measurements from axial images (LVEDV = 8.5%, LVESV = 10.8%, LVEF = 9.6%) was slightly higher than those measurements from short-axis reformations (LVEDV = 7.2%, LVESV = 9.5%, LVEF = 8.7%). The mean total evaluation time was significantly shorter using axial images (14.1 +/- 3.9 min) compared with short-axis reformations (16.9 +/- 5.2 min) (p < 0.05). CONCLUSION: Determination of LV volumes and assessment of global LV function from axial MDCT image reformations is feasible and time efficient. This approach might be a clinically useful alternative to established short-axis-based measurements in patients with normal or near-normal LV function. A progressive underestimation of LVEF with increasing LV volumes may limit the clinical applicability of the axial approach in patients with dilated cardiomyopathy.
BACKGROUND/AIM: Patients with ventricular ectopy from the right ventricular (RV) outflow tract (RVOT) are often referred for RV angiography to exclude disorders such as arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). This is usually based on a qualitative assessment of the wall motion. We present a method to quantify the wall motion and to apply this method to compare patients with RVOT ectopy to normal subjects. METHODS: RV angiograms were analyzed from 19 normal subjects and 11 subjects with RVOT ventricular arrhythmias (RVOT arrhythmia subjects) who had no other clinical or other evidence for ARVC/D. By a newly developed computer-based method, RV contours were first traced from multiple frames spanning the entire cardiac cycle. The fractional change in area between contours was then calculated as a serial function of time and location to determine both total contour area change and timing of contour movement. Contour area strain, defined as the differential change in area between nearby regions, was also computed. RESULTS: The contour area change was greatest in the tricuspid valve region and least in the RVOT and midanterior regions. The onset of contraction was earliest in the RVOT region and latest in the apical, inferior, inferoapical, and subtricuspid valve regions. The contour strain was largest in superior tricuspid valve and inferior wall and near zero within the lateral tricuspid valve region. There were significant pairwise differences in contraction area, timing, and strain in the various regions. There were no significant differences between normal subjects and RVOT arrhythmia subjects. CONCLUSIONS: The RV wall motion is nonuniform in contour area change, strain, and timing of motion. Patients with RVOT ventricular ectopy demonstrate wall motion parameters similar to those of normal subjects. This technique should be applicable in analyzing RV wall motion in patients suspected of having ARVC/D.
OBJECTIVES: This prospective study tested whether Doppler echocardiographic variables add incremental value to QRS duration in determining the prognosis of patients with chronic heart failure (CHF) and systolic dysfunction. BACKGROUND: Diastolic dysfunction frequently is observed in patients with CHF, but its prognostic impact relative to that of QRS duration is unknown. METHODS: A total of 193 patients with CHF and an ejection fraction <45% were enrolled prospectively. Echo measurements included left ventricular dimensions/volumes, ejection fraction, mitral early/late diastolic velocity ratio, deceleration time, and tissue Doppler mitral annular velocities. The mitral filling pattern was classified as either restrictive (RFP) or nonrestrictive. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point. RESULTS: During a follow-up of 385 +/- 270 days, 24 patients suffered an event (cardiac death, n = 21; urgent transplantation, n = 3). The RFP, QRS duration, left ventricular systolic diameter, and mitral annular early diastolic velocity were independent predictors of an event. In patients with QRS duration >144 ms, the outcome was markedly poorer in the presence of RFPs as compared with their absence. Similarly, despite a QRS duration <or =144 ms, the outcome was worse in the presence of a RFP. A risk-stratification model based on the three strongest independent predictors separated groups into those with good prognosis and those with high, intermediate, and low event-free survival rates. CONCLUSIONS: In subjects with CHF and systolic dysfunction, transmitral flow patterns add incremental value to QRS duration in determining the prognosis.
The diagnostic usefulness of the mitral E/E' ratio (derived from tissue Doppler imaging) as an estimate of left ventricular filling pressures was studied in 28 patients with diastolic heart failure (defined by heart failure signs and symptoms but with preserved ejection fraction) and in 46 patients with systolic heart failure (heart failure signs and symptoms and reduced ejection fraction). E/E' was reflective of filling pressures in subjects with diastolic and systolic heart failure and may be of special use in ruling out elevated filling pressures in subjects with suspected diastolic heart failure.
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BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals. METHODS AND RESULTS: A total of 212 individuals (mean age, 45+/-6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had > or =1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3+/-1.2 mm in symptomatic patients and 1.9+/-1.5 mm in asymptomatic individuals (P=0.04). During a mean follow-up of 40+/-50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome. CONCLUSIONS: The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.
BACKGROUND: The prognostic value of tissue Doppler imaging (TDI) in patients with chronic congestive heart failure (CHF) has not been compared against conventional measures of systolic, diastolic and overall left ventricular LV performance. The aim of this study was to assess the prognostic value of TDI-derived parameters in patients with CHF. METHODS: One hundred thirty-two subjects with chronic CHF [due to ischemic (n=82) or dilated (n=50) cardiomyopathy, 101 males, mean age 57+/-11 years] underwent conventional two-dimensional/Doppler echocardiography and assessment of the Tei-index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic, early and late diastolic mitral annular velocities (S', E' and A') were derived from pulsed TDI. A cardiac event (cardiac death, urgent cardiac transplantation or hospitalization due to decompensated CHF) was defined as the combined study endpoint. RESULTS: The patients were followed for a mean of 224+/-123 days. Thirty-one patients suffered an event (cardiac death, n=5; urgent cardiac transplantation, n=2; hospitalization due to CHF, n=24). In patients with event, ejection fraction was lower (25+/-10 vs. 32+/-9%), mitral deceleration time was shorter (138+/-58 vs. 193+/-72 ms), and the peak mitral E/E'-ratio (16.1+/-6.6 vs. 10.6+/-5.0) was significantly elevated as compared to patients free of events (p<0.001 for all comparisons). In those patients, the Tei-index was elevated (1.09+/-0.39 vs. 0.86+/-0.26, p<0.01), and a restrictive mitral filling pattern was more frequent (51.6 vs. 17.5%, p<0.001). Stepwise multivariate analysis identified the mitral E/E'-ratio (p<0.001) and the Tei-index (p=0.019) as the only independent predictors of a combined event. E/E'-ratio was the best predictor of hospitalization due to CHF also. In patients with mitral E/E'-ratio>12.5 or Tei-index>0.90, outcome was poor. CONCLUSIONS: In subjects with chronic CHF, the mitral E/E'-ratio is a stronger predictor of future cardiac events than conventional parameters of systolic, diastolic or overall LV performance. The E/E'-ratio may be a useful addition in the routine follow-up of such patients.