Christian Bruch

Doppler tissue analysis of mitral annular velocities: evidence for systolic abnormalities in patients with diastolic heart failure

BACKGROUND The presence of signs and symptoms of heart failure (HF), abnormal diastolic function and an ejection fraction > 45%, have been defined as diastolic HF (DHF). However, a cut-off value of 45% for ejection fraction seems arbitrary as mild systolic dysfunction may be overlooked. It was the goal of this study to assess the additive information derived from Doppler tissue imaging for patients with DHF. METHODS As a measure of left ventricular (LV) long-axis function, systolic and diastolic velocities of the mitral annulus (peak, peak early, and peak late) derived from pulsed Doppler tissue imaging were assessed in 36 asymptomatic control subjects, 36 patients with DHF, and 35 patients with systolic HF (SHF). As a measure of overall LV performance, the Tei index (isovolumic contraction time and isovolumic relaxation time divided by ejection time) was assessed. RESULTS In the DHF group, peak systolic annular velocity was reduced (7.1 +/- 1.2 cm/s) as compared with the control group (9.0 +/- 1.2 cm/s, P <.05), and was even lower in the SHF group (5.0 +/- 0.7 cm/s, P <.01 SHF group vs DHF/control groups). The Tei index was increased in the DHF group (0.53 +/- 0.14) in comparison with the control group (0.39 +/- 0.07, P <.05), and was highest in the SHF group (0.94 +/- 0.43, P <.01 SHF group vs control/DHF groups). Using peak systolic annular velocity < 7.95 cm/s as a cut-off value (derived from receiver operating characteristic curve analysis), patients with DHF were separated from control subjects with a sensitivity of 83% and a specificity of 83%. A Tei index > 0.43 separated patients with DHF and control subjects with a sensitivity of 79% and a specificity of 72%. CONCLUSION Systolic long-axis LV function is also impaired in patients with DHF, resulting in feasible diagnosis of DHF by Doppler tissue imaging analysis of LV long-axis function and overall LV function with the Tei index.

Value of Cardiovascular Magnetic Resonance Stress Perfusion Testing for the Detection of Coronary Artery Disease in Women

OBJECTIVES We wanted to assess the value of cardiovascular magnetic resonance (CMR) stress testing for evaluation of women with suspected coronary artery disease (CAD). BACKGROUND A combined perfusion and infarction CMR examination can accurately diagnose CAD in the clinical setting in a mixed gender population. METHODS We prospectively enrolled 147 consecutive women with chest pain or other symptoms suggestive of CAD at 2 centers (Duke University Medical Center, Robert-Bosch-Krankenhaus). Each patient underwent a comprehensive clinical evaluation, a CMR stress test consisting of cine rest function, adenosine-stress and rest perfusion, and delayed-enhancement CMR infarction imaging, and X-ray coronary angiography within 24 h. The components of the CMR test were analyzed visually both in isolation and combined using a pre-specified algorithm. Coronary artery disease was defined as stenosis > or =70% on quantitative analysis of coronary angiography. RESULTS Cardiovascular magnetic resonance imaging was completed in 136 females (63.0 +/- 11.1 years), 37 (27%) women had CAD on coronary angiography. The combined CMR stress test had a sensitivity, specificity, and accuracy of 84%, 88%, and 87%, respectively, for the diagnosis of CAD. Diagnostic accuracy was high at both sites (Duke University Medical Center 82%, Robert-Bosch-Krankenhaus 90%; p = 0.18). The accuracy for the detection of CAD was reduced when intermediate grade stenoses were included (82% vs. 87%; p = 0.01 compared the cutoff of stenosis > or =50% vs. > or =70%). The sensitivity was lower in women with single-vessel disease (71% vs. 100%; p = 0.06 compared with multivessel disease) and small left ventricular mass (69% vs. 95%; p = 0.04 for left ventricular mass < or =97 g vs. >97 g). The latter difference was even more significant after accounting for end-diastolic volumes (70% vs. 100%; p = 0.02 for left ventricular mass indexed to end-diastolic volume < or =1.15 g/ml vs. >1.15 g/ml). CONCLUSIONS A multicomponent CMR stress test can accurately diagnose CAD in women. Detection of CAD in women with intermediate grade stenosis, single-vessel disease, and with small hearts is challenging.

Changes in QRS voltage in cardiac tamponade and pericardial effusion: reversibility after pericardiocentesis and after anti-inflammatory drug treatment

OBJECTIVES The goal of this study was to define the association between low QRS voltage and cardiac tamponade or pericardial effusion and to assess the reversibility of low QRS voltage after therapeutic procedures. BACKGROUND It is unclear whether low QRS voltage is a sign of cardiac tamponade or whether it is a sign of pericardial effusion per se. METHODS In a prospective study design, we recorded consecutive 12-lead electrocardiograms and echocardiograms in 43 patients who were referred to our institution for evaluation and therapy of a significant pericardial effusion. Cardiac tamponade was present in 23 patients (53%). Low QRS voltage (defined as maximum QRS amplitude <0.5 mV in the limb leads) was found in 14 of these 23 subjects (61%). Nine of these 14 patients were treated by pericardiocentesis (group A). Five patients received anti-inflammatory medication (group B). Group C consisted of nine patients with pericarditis and significant pericardial effusion who had no clinical evidence of tamponade. RESULTS In group A, low QRS voltage remained largely unchanged immediately after successful pericardiocentesis (0.36 +/- 0.17 mV before vs. 0.42 +/- 0.21 mV after, p = NS), but QRS amplitude recovered within a week (0.78 +/- 0.33 mV, p < 0.001). In group B, the maximum QRS amplitude increased from 0.40 +/- 0.20 mV to 0.80 +/- 0.36 mV (p < 0.001) within six days. In group C, all patients had a normal QRS amplitude initially (1.09 +/- 0.55 mV) and during a seven-day follow-up (1.10 +/- 0.56 mV, p = NS). CONCLUSIONS Low QRS voltage is a feature of cardiac tamponade but not of pericardial effusion per se. Our findings indicate that the presence and severity of cardiac tamponade, in addition to inflammatory mechanisms, may contribute to the development of low QRS voltage in patients with large pericardial effusions.

Tissue Doppler Imaging: A New Technique for Assessment of Pseudonormalization of the Mitral Inflow Pattern

Left ventricular diastolic dysfunction (LVDD) is a frequent cause of heart failure. Doppler echocardiography has become the method of choice for the noninvasive evaluation of LVDD. However, pseudonormalization (PN) of the mitral inflow often presents a diagnostic challenge in clinical practice. In this setting, we sought to define the role of tissue Doppler imaging (TDI) of the septal mitral annulus. Echocardiography was performed in 36 consecutive subjects (age 59 ± 10 years). Eighteen of these had diagnosed coronary artery disease (CAD) with recent onset of symptoms (within 3 months), 18 had clinical suspicion of CAD, and 15 had symptoms of heart failure (New York Heart Association [NYHA] Class 2.4 ± 0.5). The mitral inflow profile (E, A, E/A) was measured by pulsed Doppler, and the deceleration time (DT) and the isovolumic relaxation time (IVRT) were calculated. Peak diastolic velocities of the septal mitral annulus (ET, AT, ET/AT) and the time interval from Q in the ECG to the onset of ET were derived from pulsed TDI. Left heart catheterization was performed for direct measurement of left ventricular end‐diastolic pressure (LVEDP). PN defined by an E/A ratio > 1 and an LVEDP ≥ 16 mmHg was found in nine patients. All patients with PN had symptoms of heart failure (NYHA Class 2.8 ± 0.5). Patients with and without PN did not differ with respect to the E/A ratio (1.29 ± 0.44 vs 1.16 ± 0.23, P = ns), DT (182 ± 38 msec vs 205 ± 42 msec, P = ns), and IVRT (88 ± 24 msec vs 92 ± 18 msec, P = ns). In the group with PN, a significant reduction of ET (5.6 ± 1.8 cm/sec vs 8.8 ± 2.9 cm/sec, P < 0.05) and ET/AT (0.5 ± 0.16 vs 0.82 ± 0.37, P < 0.05) was detected. In the PN group, the Q‐ET interval was prolonged (404 ± 48 msec vs 346 ± 50 msec, P < 0.05). Receiver operating characteristic curve analysis for ETyielded an area under the curve of 0.78 ± 0.06 (P = 0.034) for separating patients with versus without PN. When the combination of ET < 7 cm/sec and ET/AT < 1 was used as cutpoint, PN could be identified with a sensitivity of 83% and a specificity of 79%. There was no significant relation between LVEDP and either ET (r = 0.32, P > 0.2) or the Q‐ET interval (r = 0.14, P > 0.5). In conclusion, ET and the Q‐ET interval appear to be useful parameters for assessing LV diastolic dysfunction in symptomatic patients with a pseudonormal mitral inflow pattern and elevated filling pressures.

The effect of high thoracic epidural anesthesia on systolic and diastolic left ventricular function in patients with coronary artery disease.

In patients with coronary artery disease, vasoconstriction is induced through activation of the sympathetic nervous system. Both α1- and α2-adrenergic epicardial and microvascular constriction are potent initiators of myocardial ischemia. Attenuation of ischemia has been observed when sympathetic nervous system activity is inhibited by high thoracic epidural anesthesia (HTEA). However, it is still a matter of controversy whether establishing HTEA may correspondingly translate into an improvement of left ventricular (LV) function. To clarify this issue, LV function was quantified serially before and after HTEA using a new combined systolic/diastolic variable of global LV function (myocardial performance index [MPI]) and additional variables that more specifically address systolic (e.g., fractional area change) or diastolic function (e.g., intraventricular flow propagation velocity [Vp]). High thoracic epidural catheters were inserted in 37 patients scheduled for coronary artery surgery, and HTEA was administered in the awake patients. Echocardiographic and hemodynamic measures were recorded before and after institution of HTEA. HTEA induced a significant improvement in diastolic LV function (e.g., Vp changed from 45.1 ± 16.1 to 53.8 ± 18.8 cm/s; P < 0.001), whereas indices of systolic function did not change. The change in the diastolic characteristics caused the MPI to improve from 0.51 ± 0.13 to 0.35 ± 0.13 (P < 0.001). We conclude that an improvement in cardiac function was due to improved diastolic characteristics.

Usefulness of motion patterns identified by tissue Doppler echocardiography for diagnosing various cardiac masses, particularly valvular vegetations

This study sought to test whether anomalous cardiac and aortic structures can be differentiated from native tissue and artifacts by physical properties of tissue motion using transesophageal tissue Doppler echocardiography (TDE). TDE was employed in 85 consecutive patients after anomalous structures had been detected by conventional transesophageal echocardiography (TEE). The control group consisted of 40 randomized patients. Certainty of diagnosis was divided into 4 categories, and TDE signals were related to particular anomalous structures by a blinded second observer. A mechanical model of a beating ventricle was constructed and suspended in a water bath. Synthetic material was utilized to simulate anomalous intracavitary structures with varying shape, consistency, and attachment. Incoherent motion was present in endocarditic vegetations, freely oscillating thrombi, fourth-degree aortic plaques, Chiari network, valvular prolapse, tumors, and in normal valve leaflets and papillary muscles. Within 15 seconds vegetations could be detected in 17 patients (68%) using TDE versus 5 patients (20%) using only conventional imaging. Coherent motion with a phase difference occurred due to damped oscillation. This phenomenon occurred in 5 patients with thrombi of the left atrial appendage (100%), in 3 ventricular clots (75%), and in 2 hypernephroma in the right atrium (100%). Rapid identification of clots could be achieved in 15 patients (71%) versus 12 patients (57%). Concordant motion was shown in third-degree aortic plaques, postrheumatic valvular lesions, and aortic intramural hematomas, but diagnostic benefit could not be demonstrated. In 41 patients (48%) histopathologic and intraoperative results confirmed echocardiographic findings. Motion patterns could be reproduced independently of the heart rate by model experiments. This study demonstrates that TDE expedites the detection of vegetations in infective endocarditis. Diagnostic certainty can be increased as well for thrombus formations.

Diastolic filling pattern and left ventricular diameter predict response and prognosis after cardiac resynchronisation therapy

Objective: To investigate predisposing factors for cardiac resynchronisation therapy (CRT) response. Design: Single-centre study. Setting: University hospital in Germany. Patients: 122 consecutive patients with heart failure (mean (SD) age 65 (11) years; ischaemic/non-ischaemic 41%/55%; New York Heart Association (NYHA) class 3.1 (0.3); left ventricular ejection fraction 24.4 (8.1)%; QRS width 170 (32) ms, quality of life (QoL) 43.5 (19.2)) with an indication for CRT and demonstrated left ventricular dyssynchrony by echocardiography including tissue Doppler imaging. Interventions: Besides laboratory testing of clinical variables, results of ECG, echocardiography including tissue Doppler imaging, invasive haemodynamics, measures of QoL and of exercise capacity were obtained before CRT implantation and during follow-up. Main outcome measure: Responders were predefined as patients with improvement by one or more NYHA functional class or reduction of left ventricular end-systolic volume by 10% or more during follow-up. Mean (SD) follow-up was 418 (350) days. Results: Overall, 70.5% of patients responded to CRT. Responders had a significantly improved survival compared with non-responders (96.2% vs 45.5%, log-rank p<0.001). On univariate analysis, left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), E/A ratio, a restrictive filling pattern, mean pulmonary artery pressure, pulmonary capillary pressure, N-terminal pro-brain natriuretic peptide and Vo2max were significant predictors of outcome. On multivariate analyses, LVESD (p = 0.009; F = 7.83), pulmonary capillary pressure (p = 0.015, F = 6.61) and a restrictive filling pattern (p = 0.026, F = 5.707) remained significant predictors of response. Conclusions: Despite treatment according to present guidelines nearly 30% of patients had no benefit from CRT treatment in a clinical setting. On multivariate analyses, patients with an increased left ventricular end-systolic diameter and concomitant diastolic dysfunction had a significantly worse outcome.

Tei-Index in coronary artery disease--validation in patients with overall cardiac and isolated diastolic dysfunction.

Hintergrund Der Index „Isovolumetrische Kontraktionszeit + Isovolumetrische Relaxationszeit/Austreibungszeit“ („Tei-Index“) liefert wichtige Informationen über den Grad der kardialen Funktionsstörung und besitzt prognostische Bedeutung bei Patienten mit dilatativer Kardiomyopathie und kardialer Amyloidose. Die diagnostische Wertigkeit des Index bei Patienten mit koronarer Herzerkrankung (KHK) ist unklar. Ziel der vorliegenden Studie war die Validierung des Tei-Index bei KHK-Patienten mit globaler kardialer Funktionsstörung und isolierter diastolischer Dysfunktion. Methoden&>;Ergebnisse In die Studie eingeschlossen wurden 60 Patienten, bei denen im Rahmen der Linksherzkatheterisierung der enddiastolische Ventrikeldruck (LVEDP) gemessen wurde: 20symptomatische KHK-Patienten mit globaler kardialer Funktionsstörung (definiert als linksventrikuläre Ejektionsfraktion (EF) <45% (im Mittel 27±8%) und LVEDP≥16mmHg (im Mittel 22±6mmHg), NYHA-Stadium 2,7±0,4, GKF-Gruppe), 29 symptomatische KHK-Patienten mit isolierter diastolischer Dysfunktion (EF>45% (im Mittel 55±8%), normaler enddiastolischer Ventrikeldurchmesser (im Mittel 2,8±0,4cm/m2) und LVEDP≥16mmHg (im Mittel 22±6mmHg), NYHA-Stadium 2,3±0,4, IDD-Gruppe) und 11asymptomatische Kontrollprobanden (EF 65±9%, LVEDP 11±4mmHg, KON-Gruppe). Nach Durchführung einer konventionellen zweidimensionalen und dopplerechokardiographischen Untersuchung wurde der Tei-Index gemessen.    Der Tei-Index war bei allen Probanden einfach und reproduzierbar abzuleiten. Im Vergleich zur KON-Gruppe waren die isovolumetrische Kontraktionszeit in der GKF-Gruppe verlängert, und die Austreibungszeit verkürzt, sodass der Tei-Index bei GKF-Patienten signifikant erhöht war (0,71±0,28 vs. 0,40±0,11, p<0,01). In der IDD-Gruppe waren die isovolumetrische Relaxationszeit verlängert und die isovolumetrische Kontraktionszeit verkürzt, sodass der Wert des Tei-Index bei normaler Austreibungszeit im Vergleich zur Kontroll-Gruppe im Wesentlichen unverändert blieb (0,45±0,14 vs. 0,40±0,11, p=ns). Die „Receiver-Operating-Characteristic“-Kurvenanalyse für den Tei-Index ergab eine Fläche unter der Kurve von 0,92±0,04 für die Trennung von Patienten mit und ohne globale kardiale Funktionsstörung. Für einen Tei-Index >>;0,49 als Cut-Off-Wert betrug die Sensitivität zur Erfassung von GKF-Patienten 96%, während die Spezifität bei 86% lag. Schlussfolgerung The Tei-Index ist ein valider und einfach abzuleitender Parameter zur Erfassung symptomatischer KHK-Patienten mit globaler kardialer Funktionsstörung. Bei symptomatischen KHK-Patienten mit isolierter diastolischer Dysfunktion ist der diagnostische Nutzen des Index eingeschränkt. Background The index „isovolumic contraction time and isovolumic relaxation time divided by ejection time” („Tei-Index”) has been demonstrated to provide useful information about disease severity and prognosis in patients with dilated cardiomyopathy and cardiac amyloidosis. In patients with coronary artery disease (CAD), the diagnostic utility of this index is unclear. We attempted to validate the Tei-Index in CAD patients with overall cardiac or isolated diastolic dysfunction. Methods and results Sixty subjects were included who underwent left heart catheterization for invasive measurement of left ventricular end-diastolic pressure (LVEDP): 20 symptomatic CAD patients with overall cardiac dysfunction (defined by a LV ejection fraction (EF) <45% (mean 27±8%) and a LVEDP≥16mmHg, (mean 22±6mmHg), NYHA class 2.7±0.4, OCD group), 29 symptomatic CAD patients with isolated diastolic dysfunction (defined by an EF >45% (mean 55±8%), a normal end-diastolic diameter index (mean 2.8±0.4 cm/m2) and a LVEDP≥16mmHg (mean 22±6mmHg), NYHA class 2.3±0.4, IDD group) and 11 asymptomatic control subjects (EF 65±9%, LVEDP 11±4mmHg, CON group). After conventional 2-D- and Doppler echocardiographic examination, the Tei-Index was obtained.    The Tei-Index was easily and reproducibly measured in all study subjects. In the OCD group, isovolumic contraction time was prolonged and ejection time was shortened in comparison to the CON group, resulting in a significantly increased Tei-Index (0.71±0.28 vs 0.40±0.11, p<0.01). In the IDD group, isovolumic relaxation time was prolonged and isovolumic contraction time was shortened in comparison to controls, resulting in a largely unchanged Tei-Index (0.45±0.14, p=ns). Receiver operating characteristic curve analysis for the Tei-Index yielded an area under the curve of 0.92±0.04 for separating patients with vs without OCD. Using a Tei-Index >>;0.49 as a cut-off, OCD patients were identified with a sensitivity of 96% and a specificity of 86%. Conclusion The Tei-Index is a valid and readily derived indicator of global cardiac dysfunction in CAD patients with impaired systolic and diastolic LV performance. The use of this index seems to be limited in CAD patients with primary diastolic dysfunction.

Comparison of the Prognostic Usefulness of N-Terminal Pro-Brain Natriuretic Peptide in Patients With Heart Failure With Versus Without Chronic Kidney Disease

In patients with chronic heart failure (CHF), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicted poor outcome. Clinical predictors of NT-pro-BNP and its usefulness in the presence of chronic kidney disease (CKD) are largely unknown. A total of 341 patients with stable CHF were enrolled, of whom 183 (54%) had CKD. During a follow-up of 620 +/- 353 days, 57 patients (17%) experienced a cardiac event (cardiac death, need for extracorporeal assist device, or urgent cardiac transplantation), and 64 patients (20%) were rehospitalized because of worsening CHF. NT-pro-BNP was related to New York Heart Association functional class (R = 0.44, p <0.001) and inversely related to ejection fraction (R = -0.52, p <0.001) and glomerular filtration rate (R = -0.32, p <0.001). A cardiac event was independently predicted by NT-pro-BNP (hazard ratio [HR] 1.56, p <0.001), ejection fraction (HR 0.95, p = 0.018), and serum sodium (HR 0.89, p = 0.004). Using receiver-operator characteristic analysis, NT-pro-BNP > or =1,474 pg/ml best separated patients with or without cardiac events. In patients without CKD, outcome was significantly worse in patients with NT-pro-BNP >1,474 pg/ml in comparison to patients with NT-pro-BNP <1,474 pg/ml (event-free survival rate 0% vs 75%; p <0.001). In patients with CKD, outcome was also significantly worse in subjects with NT-pro-BNP >1,474 pg/ml in comparison to those with NT-pro-BNP <1,474 pg/ml (event-free survival rate 48% vs 93%; p <0.001). NT-pro-BNP independently predicted rehospitalization caused by worsening CHF (HR 1.26, p = 0.023), and a cut-off value of 1,474 pg/ml also separated patients with poor and intermediate prognosis in the CKD and non-CKD groups. In conclusion, NT-pro-BNP independently predicted morbidity and mortality in patients with CHF with and without CKD.

Reduced repolarization reserve due to anthracycline therapy facilitates torsade de pointes induced by IKr blockers

BackgroundCytostatic agents such as anthracyclines may cause changes in the electrophysiologic properties of the heart. We hypothesized that anthracyclines facilitate life-threatening proarrhythmic side effects of cardiovascular and non-cardiovascular repolarization prolonging drugs.Methods and resultsThe electrophysiologic effects of chronic administration of doxorubicin (Dox) were studied in ten rabbits, which were treated with Dox twice a week (1.5 mg/kg i. v.). A control group (11 rabbits) was given NaCl solution. Two of ten Dox rabbits died suddenly, the remaining animals showed mild clinical signs of heart failure after a period of six weeks. Echocardiography demonstrated a decrease in ejection fraction (pre treatment: 74 ± 23% to post treatment: 63 ± 16% (p <0.05)). In isolated hearts, action potential duration measured by eight simultaneously recorded monophasic action potentials (MAP) was similar in Dox and control hearts. However, in Dox rabbits, administration of the IKr–blocker erythromycin (150–300 μM) led to a significant greater prolongation of the mean MAP duration (63 ± 21ms vs 29 ± 12 ms, p <0.05) and the QT interval (100 ± 32ms vs 58 ± 17 ms, p <0.05) as compared to control. Moreover, IKr–block led to a more marked increase of dispersion of MAP90 in the Dox group as compared to control hearts (23 ± 7ms vs. 9 ± 4 ms). In the presence of hypokalemia more episodes of early afterdepolarizations and torsade de pointes occurred (p <0.05).ConclusionEven during the early phase of chemotherapeutic treatment,before significant QT-prolongation is present,anthracyclines lead to an increased sensitivity to the proarrhythmic potency of IKr-blocking drugs. Thus, anthracycline therapy reduces repolarization reserve and thereby represents a novel contributing factor for the development of lifethreatening proarrhythmia.