Influence of left bundle branch block on left ventricular volumes, ejection fraction and regional wall motion.

BACKGROUND.: Left ventricular volumes, ejection fraction and regional wall motion are cardiac parameters which provide valuable information for patient management in a large variety of cardiac conditions. Differences in regional wall motion are of relevance in the field of cardiac resynchronisation therapy. We quantified three-dimensional echocardiographic measurements of left ventricular volumes, ejection and regional wall motion (e.g. expressed as systolic dyssynchrony index (SDI)) in two patient cohorts: patients with normal conduction and patients with complete left bundle branch block. METHODS.: Thirty-five patients scheduled for routine cardiac examination underwent three-dimensional echocardiography: 23 patients with normal conduction and 12 patients with a complete left bundle branch block. Full-volume datasets were analysed and end-systolic volume (ESV), end-diastolic volume (EDV) and ejection fraction (EF) were obtained. SDI was derived from the standard deviation of the measured times to reach minimal regional volume for each of the 16 segments of the left ventricle. RESULTS.: A significant difference was observed in left ventricular volumes, ejection fraction and SDI between the two groups. Patients with complete left bundle branch block showed higher EDV (p=0.025) and ESV (p<0.01) and a lower EF (p<0.01) than patients with normal conduction. SDI is significantly higher in patients with complete left bundle branch block (p=0.004) expressing a higher amount of ventricular dyssynchrony. Intraobserver variability showed excellent correlation coefficients: r=0.99 for EDV, ESV and SDI and r=0.98 for EF. CONCLUSION.: Three-dimensional echocardiography is a feasible and reproducible method for the quantification of left ventricular volumes, left ventricular ejection fraction and regional wall motion. Differences can be assessed between normal patients and patients with left bundle branch block. (Neth Heart J 2007;15:89-94.).

Cardiac 123 I-MIBG imaging and clinical variables in risk stratification in patients with heart failure treated with beta blockers.

Both myocardial m-[123I]iodobenzylguanidine (123I-MIBG) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis. However, these observations were noted before treatment with beta blockers became part of standard clinical practice. Fifty-eight patients with chronic heart failure (New York Heart Association functional class II and III, ejection fraction <35%; 53% ischaemic cardiomyopathy) were prospectively studied with a mean follow-up of 36 months. During the observational period, 17 patients (29.3%) had a predefined event (death and heart transplantation). All prognostic parameters were obtained before beta blocker therapy was initiated. In both uni- and multivariate analysis, the heart-mediastinum ratio of 123I-MIBG uptake did not correlate with cardiovascular mortality. In the multivariate Cox regression analysis, plasma norepinephrine, peak oxygen consumption, end-diastolic volume as measured by echocardiography and exercise performance during bicycling and walking had prognostic significance in patients with heart failure treated with beta blockers in addition to angiotensin-converting enzyme inhibitors.

Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure.

BACKGROUND: Sympathetic activation plays a pivotal role in heart failure attributing to the disease process and symptoms of the patient. Myocardial sympathetic activity can be visualized using radioiodinated metaiodobenzylguanidine 123I-MIBG, a structural analogue of norepinephrine (NE). AIM OF THE STUDY: We investigated whether a relation exists between myocardial MIBG uptake and different functional, hemodynamic and neurohormonal parameters in patients with chronic heart failure. METHODS AND RESULTS: The study comprised 52 patients with stable congestive heart failure functional class II or III and left ventricular ejection fractions of <35%. The heart/mediastinum ratio (H/M ratio) was calculated to quantify myocardial MIBG uptake. A significant correlation was found between peak oxygen consumption and maximal exercise duration as exercise parameters and H/M ratio of MIBG (R, respectively, 0.36 and 0.4, P<0.05). From all other measured parameters, only plasma NE showed a significant correlation with the H/M ratio of MIBG. CONCLUSION: Cardiac sympathetic activity, as measured by myocardial MIBG uptake, is correlated with peak exercise parameters.

Beta blockers in heart failure haemodynamics, clinical effects and modes of action.

Treatment for heart failure may be directed at relieving symptoms and/or improving prognosis. One of the primary aims of research in heart failure is to alter the progressive decline in pump function and thereby improve prognosis. For many years, diuretics have been known as therapeutics in heart failure and they are very effective in symptom relief. Vasodilators and inotropes also have beneficial effects on symptom relief especially in the acute phase through changes in cardiac output, filling pressures and renal perfusion. However, although these treatments produce short-term relief, none have been shown to influence the disease process and thereby improve mortality. Indeed, many of these drugs may even lead to untoward long-term clinical outcomes as has been shown for example for milrinone and ibopamine. There is overwhelming evidence that drugs interfering with the neurohormonal activation in heart failure not only produce symptomatic relief but are also capable of attenuating disease progression with concomitant reductions in both morbidity and mortality. About a decade ago, convincing and large-scale evidence showed that ACE inhibitors produced favourable effects by antagonising the activated renin-angiotensin system. More recently, ß-blockers, which antagonise the activated sympathetic system, were shown to be beneficial in the long term in moderate severe heart failure in terms of significant improvements in both morbidity and mortality. The RALES study further amplified the concept that drugs that interact in the neurohormonal system have beneficial effects. In this study, spironolactone, a weak, potassium-sparing diuretic counteracting aldosterone showed a reduction in mortality in more severe forms of heart failure.

Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure.

This study demonstrates that in patients with mild to moderate heart failure, cardiac metaiodobenzylguanidine (MIBG) washout positively correlates with normalized low-frequency power in the heart rate variability spectrum. Alterations of the cardiac sympathetic nervous system could be detected with MIBG scintigraphy in patients with normal plasma norepinephrine levels. Therefore cardiac MIBG washout may be a valuable noninvasive technique to assess early alterations in cardiac sympathetic activity that may have potential clinical implications in patients with mild to moderate heart failure.

Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.

OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference.

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([123I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [123I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [123I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [123I]MIBG planar and single-photon emission tomographic (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the 123I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31 +/- 0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4 +/- 2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [123I]MIBG uptake.

Protocols for selection of cardiac radionuclide studies for use as a data base of normal studies and typical patterns of diseases. COST B2 Working Group II, in association with relevant working/task groups of the European Association of Nuclear Medicine and the European Society of Cardiology.

A data base of clinical studies is required for quality assurance of software used for analysis of radionuclide cardiac imaging procedures. Studies used must be rigorously validated in terms of both the clinical condition of the patient undergoing the procedure and the imaging protocol used. Selection protocols for the creation of a software phantom data base of normal studies and three typical patterns of cardiac disease--recent transmural myocardial infarction, isolated myocardial ischaemia and dilated cardiomyopathy--have been developed by the Cardiac Working Group of the European COST B2 project in association with the Cardiac Task Group of the European Association of Nuclear Medicine and the Working Group on Nuclear Cardiology of the European Society of Cardiology. These protocols include criteria for the interpretation of qualitative and quantitative non-radionuclide data. Compliance of the clinical data with the selection criteria will have to pass scrutiny by an international team for each study used as a software phantom. The radionuclide studies encompass stress and rest myocardial perfusion studies (planar and single photon emission tomography) using thallium-201 and technetium-99m methoxyisobutylisonitrile and rest gated blood pool studies. Methods for acquisition of data are defined for each type of study and for each individual study a portfolio of all clinical data is established. A pilot study is required to investigate the problems and logistics of distributing clinical radionuclide studies between a range of computers and institutes, and to ascertain the procedures necessary for analytical comparison of the results obtained.

Long-term efficacy of continuous and intermittent use of transdermal nitroglycerin in stable angina pectoris.

To assess efficacy of transdermal nitrate use, a randomized, placebo-controlled trial of continuous and intermittent use of nitroglycerin patches (10 mg/24 hours) was conducted in 127 patients with stable angina pectoris who discontinued exercise testing within 9 minutes because of angina. After a placebo run-in week, baseline (day 0) symptom-limited exercise testing was performed and repeated on day 1 and 14 before and after the administration of 0.5 mg of sublingual nitroglycerin. On day 0, total exercise duration was the same (within narrow limits) in all 3 groups and remained unchanged in the placebo group. On day 1, total exercise duration increased from 406 +/- 115 to 469 +/- 158 seconds (p less than 0.001) in the continuously treated group and from 396 +/- 105 to 475 +/- 171 seconds (p less than 0.001) in the intermittently treated group. In the intermittent group, exercise duration increased slightly to 483 +/- 140 seconds on day 14, and in the continuous group exercise duration decreased to 447 +/- 144 seconds. However, this decrease was not statistically significant. Similar treatment effects were seen for time to 1-mm ST depression. Sublingual nitroglycerin remained effective in all 3 groups and on all days. Eleven actively treated patients and 1 patient taking placebo discontinued the study because of headache. It is concluded that continuous use of transdermal nitroglycerin remains partially effective and intermittent therapy remains fully effective in improving long-term exercise capacity with acceptable adverse effects in patients with stable angina pectoris.