Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies.

BACKGROUND: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). METHODS: The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. RESULTS: By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). CONCLUSIONS: Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results.

Surgery of secondary mitral insufficiency in patients with impaired left ventricular function.

BACKGROUND: Secondary mitral insufficiency (SMI) is an indicator of a poor prognosis in patients with ischemic and dilated cardiomyopathies. Numerous studies corroborated that mitral valve (MV) surgery improves survival and may be an alternative to heart transplantation in this group of patients.The aim of the study was to retrospectively analyze the early and mid-term clinical results after MV repair resp. replacement in patients with moderate-severe to severe SMI and left ventricular ejection fraction (LVEF) below 35%. METHODS: We investigated 40 patients with poor LVEF (mean, 28 +/- 5%) and SMI who underwent MV repair (n = 26) resp. replacement (n = 14) at the University Hospital Muenster from January 1994 to December 2005. All patients were on maximized heart failure medication. 6 pts. had prior coronary artery bypass grafts (CABG). Twenty-seven patients were in New York Heart Association (NYHA) class III and 13 were in class IV. Eight patients were initially considered for transplantation. During the operation, 14 pts had CABG for incidental disease and 8 had tricuspid valve repair. Follow-up included echocardiography, ECG, and physician's examination and was completed in 90% among survivors. Additionally, the late results were compared with the survival after orthotope heart transplantation (oHTX) in adults with ischemic or dilated cardiomyopathies matched to the same age and time period (148 patients). RESULTS: Three operative deaths (7.5%) occurred as a result of left ventricular failure in one and multiorgan failure in two patients. There were 14 late deaths, 2 to 67 months after MV procedure. Progress of heart failure was the main cause of death. 18 patients who were still alive took part on the follow-up examination. At a mean follow-up of 50 +/- 34 (2-112) months the NYHA class improved significantly from 3.2 +/- 0.5 to 2.2 +/- 0.4 (p < 0.001). The LVEF improved significantly from 29 +/- 5% to 39 +/- 16 (p < 0.05). There were no differences in survival after MV repair or replacement. The 1-, 3-, 5-year survival rates in the study group were 80%, 58% and 55% respectively. In the group of patients after oHTX the survival was accordingly 72%, 68%, 66% (p > 0.05). CONCLUSION: High risk mitral valve surgery in patients with cardiomyopathy and SMI offers a real mid-term alternative method of treatment of patients in drug refractory heart failure with similar survival in comparison to heart transplantation.

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.

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.

Diagnostic usefulness and prognostic implications of the mitral E/E' ratio in patients with heart failure and severe secondary mitral regurgitation.

In patients with chronic heart failure (CHF) and severe secondary mitral regurgitation (MR), the diagnostic usefulness and prognostic impact of tissue Doppler imaging (TDI) is unknown. This prospective study enrolled 370 patients with stable CHF. Severe secondary MR, defined as effective regurgitant orifice area >/=0.20 cm(2), was present in 92 patients (25%). Echo measurements comprised left ventricular volumes, ejection fraction, mitral E/A ratio, deceleration time, and TDI-derived mitral annular velocities (e.g., S', E', A', E/E'). During a follow-up of 790 +/- 450 days, all-cause mortality and rehospitalization data were analyzed. Patients with or without MR did not differ with respect to age or ejection fraction, but patients with MR were in a poorer New York Heart Association functional class and had a higher mitral E/E' ratio. During follow-up, 70 patients (18%) died and 134 patients (36%) were rehospitalized for worsening heart failure. Mortality rate was significantly higher in patients with versus without severe MR (33% vs 14%, p <0.001). In the MR group, the mitral E/E' ratio independently predicted all-cause mortality and was also significantly associated with rehospitalization for worsening heart failure. In patients with MR with an E/E' ratio >13.5, outcome was markedly worse compared with patients with an E/E' ratio

Transmitral flow patterns and the presence of chronic kidney disease provide independent and incremental prognostic information in patients with heart failure and systolic dysfunction.

BACKGROUND: Transmitral flow patterns derived from Doppler echocardiography carry prognostic information in patients with chronic heart failure and systolic dysfunction. In such patients, chronic kidney disease (CKD) defined as a reduction in estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) is frequent, but its prognostic impact relative to that of transmitral flow patterns is unknown. METHODS: This prospective study enrolled 292 patients with stable chronic heart failure and systolic dysfunction (mean ejection fraction 30 +/- 10), of whom 148 had CKD. Echocardiographic measurements comprised left ventricular dimensions/volumes, ejection fraction, the ratio of early (E) to late (A) transmitral flow velocity, deceleration time, and tissue Doppler mitral annular velocities. The mitral filling pattern (FP) was classified as either restrictive FP (RFP) or non-RFP. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point. RESULTS: During a follow-up of 497 +/- 373 days, 45 patients had a cardiac event (cardiac death, n = 42; urgent cardiac transplantation, n = 3). On multivariate Cox analysis including clinical and echocardiographic variables, independent prognostic predictors were RFP (hazard ratio: 2.77, 95% confidence interval 1.28-6.09), CKD (hazard ratio: 2.79, 95% confidence interval 1.24-6.28), and left atrial diameter. In patients with RFP, the prognosis was markedly worse in the presence of CKD as compared with the absence (event-free survival of 23% vs 83%, P = .03). Similarly, in patients with non-RFP, outcome was worse in the presence of CKD (event-free survival of 71% vs 88%, P = .003). CONCLUSIONS: In patients with chronic heart failure and systolic dysfunction, the presence of CKD adds incremental value to transmitral flow patterns in determining the prognosis.

Prevalence and prognostic impact of comorbidities in heart failure patients with implantable cardioverter defibrillator.

AIMS: This study assessed the prevalence and the prognostic impact of comorbidities in heart failure patients with implantatable cardioverter-defibrillator (ICD). METHODS AND RESULTS: We prospectively enrolled 146 patients with chronic heart failure, an ICD, and systolic dysfunction (mean ejection fraction 29 +/- 10%). Cardiac death was chosen as the primary endpoint. Death or appropriate ICD therapy, i.e. antitachycardia pacing/shock due to sustained ventricular tachycardia or ventricular fibrillation, was chosen as the secondary endpoint. Seventy-five patients (52%) had chronic kidney disease (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 39 patients (27%) were anaemic, and 34 patients (23%) had diabetes mellitus. During a follow-up of 663 +/- 400 days, 22 patients (15%) died, and 41 patients (28%) received an appropriate ICD therapy. By multivariate Cox analysis, independent predictors of cardiac death were chronic kidney disease, age, and NYHA functional class. Death/appropriate ICD therapy were independently predicted by chronic kidney disease and QRS duration. In the presence of chronic kidney disease, outcome was significantly worse when compared with the absence (event-free survival rate 51 vs. 76%, P < 0.001). CONCLUSION: In heart failure patients with an ICD, comorbidities are frequent but only the presence of chronic kidney disease is independently associated with increased morbidity and mortality.

Impact of haemoglobin concentration and chronic kidney disease in patients with coronary heart disease undergoing percutaneous coronary interventions.

BACKGROUND: A few recent studies suggested that anaemia has a marked impact on the survival of patients with coronary heart disease (CHD). However, all of these analyses did not take into consideration that chronic kidney disease (CKD) plays an important role in erythropoiesis and anaemia. Therefore, we assessed in this study whether anaemia is an independent predictor of mortality or if its impact was confounded by CKD, which is known to have itself a marked impact on outcomes of patients with CHD. METHODS: In a retrospective cohort study, we analysed 709 patients with symptomatic and significant CHD who underwent percutaneous coronary interventions. Patients were classified as anaemic using the WHO definition; renal function was classified by the estimated glomerular filtration rate (eGFR). RESULTS: In comparison with non-anaemic patients, anaemic patients had a significantly higher in-hospital mortality (4.9 vs 0.5%, P<0.001). Moreover, 1-year mortality rates of anaemic patients were significantly higher regardless of whether they had a normal eGFR (22 vs 2.8%, P=0.029), an eGFR of 60-89 ml/min (14 vs 4.2%, P<0.001), an eGFR of 30-59 ml/min (21 vs 3.7%, P<0.001) or an eGFR<30 ml/min (26 vs 0%, NS). When cumulative mortality was analysed by haemoglobin concentrations in steps of 1 g/dl from <11.0 g/dl to >16.9 g/dl, 1-year mortality rates were 28, 18, 15, 5.5, 3.8, 5.7, 1.5 and 0%, respectively (P<0.001, log rank). Even after adjustment for comorbidities by multivariable Cox regression models, haemoglobin remained a significant predictor of long-term mortality (hazard rate ratio 0.77, 95% confidence interval (CI): 0.62-0.82, P<0.001) while eGFR was not (hazard rate ratio 1.0, 95% CI: 0.99-1.01). CONCLUSIONS: Anaemia was found to be a strong and independent predictor of acute and long-term mortality in patients with symptomatic CHD, regardless of the presence of CKD.

Calcineurin inhibitor-free immunosuppression using everolimus (Certican) in maintenance heart transplant recipients: 6 months' follow-up.

BACKGROUND: Everolimus is a proliferation signal-inhibitor recently introduced in heart transplant recipients. To date, little is known about calcineurin inhibitor (CNI)-free immunosuppression using everolimus. This study reports the results of CNI-free immunosuppression using everolimus. METHODS: During a continuous 9-month period, 60 heart transplant recipients were enrolled. Reasons for switching to everolimus were side effects associated with prior CNI immunosuppression. All patients underwent standardized switching protocols and completed 6 months of follow-up. Blood was obtained for lipid status, renal function, routine controls, and levels of immunosuppressive agents. Echocardiography and a physical examination were performed on Days 0, 14, 28, and then every 3 months. RESULTS: After switching to everolimus, most patients recovered from the side effects associated with CNIs. Renal function improved significantly after 6 months (creatinine, 2.1 +/- 0.6 vs 1.5 +/- 0.9 mg/dl, p = 0.001; creatinine clearance, 42.2 +/- 21.6 vs 61.8 +/- 23.4 ml/[min x 1.73 m2], p = 0.018). Arterial hypertension improved after 3 months and remained decreased during the observation period. Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Adverse events occurred in 8 patients (13.3%), including interstitial pneumonia (n = 2), skin disorders (n = 2), reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3). CONCLUSION: Preliminary data suggest that CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance heart transplant recipients. Arterial hypertension and renal function improved significantly. CNI-induced side effects such as tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved in most patients.

Chronic kidney disease in patients with chronic heart failure--impact on intracardiac conduction, diastolic function and prognosis.

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.

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

BACKGROUND: Cytostatic 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 RESULTS: The 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 I(Kr)-blocker erythromycin (150-300 microM) 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, I(Kr)-block led to a more marked increase of dispersion of MAP(90) 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). CONCLUSION: Even during the early phase of chemotherapeutic treatment,before significant QT-prolongation is present,anthracyclines lead to an increased sensitivity to the proarrhythmic potency of I(Kr)-blocking drugs. Thus, anthracycline therapy reduces repolarization reserve and thereby represents a novel contributing factor for the development of life-threatening proarrhythmia.

Prevalence and prognostic impact of comorbidities in patients with severe aortic valve stenosis.

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.

N-terminal pro-brain natriuretic peptide, kidney disease and outcome in patients with chronic heart failure.

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.

Risk stratification in chronic heart failure: independent and incremental prognostic value of echocardiography and brain natriuretic peptide and its N-terminal fragment.

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.

Age and gender related reference values for transthoracic Doppler-echocardiography in the anesthetized CD1 mouse.

OBJECTIVE: Doppler-echocardiography of the mouse has evolved to a commonly used technique in the past years as recent advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to murine models. Although mouse echocardiography is widely used, there is only little information on reference data for wild-type animals available, particularly in older mice. METHODS: We therefore established a database with echocardiographic reference-values in a large set of young (8 weeks) and older adult (52 weeks) Swiss type CD1-mice of either sex. We performed a complete Doppler-echocardiographic examination under light Ketamine-Xylazine-anesthesia. LV-mass was calculated and compared with necropsy heart weights to validate the LV-mass calculation. RESULTS: Doppler-echocardiographic measurements in mice were feasible to assess cardiac morphology and function. Sonomorphological and functional parameters hardly changed between the age of 12 and 52 weeks. Wall thickness, LV-mass and cardiac output were stable with aging. There was a good relative correlation between echocardiographically estimated LV-mass and necropsy heart weight although absolute values differed. There were no significant echocardiographic differences between male and female mice. CONCLUSIONS: The reference values established in this study can be useful in recording and quantifying pathological changes in murine models of cardiovascular diseases. There is hardly any change of cardiac function between the age of 12 and 52 weeks.

Prognostic value of a restrictive mitral filling pattern in patients with systolic heart failure and an implantable cardioverter-defibrillator.

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.

Left bundle branch block in chronic heart failure-impact on diastolic function, filling pressures, and B-type natriuretic peptide levels.

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.

Prognostic value of tissue Doppler imaging in patients with chronic congestive heart failure.

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.

Pericarditis constrictiva and high-degree atrioventricular block as a first manifestation of a cardiac B-cell lymphoma.

Primary cardiac lymphoma is an extremely rare extranodal non-Hodgkin's lymphoma, exclusively located in the heart and/or the pericardium with no evidence of extracardiac dissemination. In this report, we describe a cardiac B-cell lymphoma arising in a 70-year-old woman who presented to the hospital with heart failure symptoms and a high-degree atrioventricular block of unknown origin. Echocardiography revealed a massive infiltrative thickening of the atrial septum, the aortic root, and the pericardium. Pulsed wave and Doppler tissue findings were highly suggestive for pericarditis constrictiva. Positron emission tomography showed unusually strong metabolic activity in the atrial septum, both atria, and the entire pericardium. Suggested malignoma was confirmed by the pericardial biopsy specimens, which revealed a high-grade diffuse CD20+ B-cell lymphoma.

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 alpha1- and alpha2-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.