Klaus K. Witte

Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging.

OBJECTIVE Quantitative 2-dimensional color Doppler tissue imaging is a new method to reveal impairment of left ventricular (LV) and right ventricular (RV) longitudinal function, which is a potential marker of early myocardial disease. The aim of this study was to obtain normal values for atrioventricular annular and regional myocardial velocities using this method. METHODS A total of 123 healthy patients (age range: 22 to 89 years) underwent echocardiography including color Doppler tissue imaging using a scanner (Vivid 5, GE Vingmed, Horten, Norway) with postprocessing analysis (Echopac 6.3, GE Vingmed). Regional myocardial velocities were measured at 12 LV segments in 3 apical views and 2 segments of the free RV wall. Mitral annular velocities from 6 sites, and tricuspid annular velocities at its lateral site, were also assessed. At each site, systolic (S(m)), early diastolic (E(m)), and late diastolic (A(m)) velocities were measured, and the E(m)/A(m) ratio was calculated. RESULTS Patients were classified into 4 groups aged 20 to 39, 40 to 59, 60 to 79, and >/=80 years. Mitral annular velocity and regional LV myocardial S(m) and E(m) progressively decreased with age. A(m), whereas low in the youngest age group, increased significantly in patients more than 40 years of age. The E(m)/A(m) ratio gradually declined with aging. There were no differences between age groups in S(m) measured at the tricuspid annulus and free RV wall, but the pattern of age-related changes of diastolic velocities and E(m)/A(m) ratio was the same as in the LV. Slight but significant sex-related differences were observed in middle-aged groups. The intraobserver and interobserver reproducibility was highest for atrioventricular annular velocities. CONCLUSIONS A progressive decrease in S(m) reveals a decline in longitudinal systolic LV function with age, whereas systolic RV function remains unaffected. Atrioventricular annular velocity and regional E(m) decrease with aging in both ventricles, suggesting a deterioration in the diastolic properties of the myocardium, whereas A(m) increases from middle age implying a compensatory augmentation of atrial function. The study results can be used as reference data for the quantitative assessment of longitudinal LV and RV function in patients with cardiac disease.

Chronic heart failure and micronutrients

Heart failure (HF) is associated with weight loss, and cachexia is a well-recognized complication. Patients have an increased risk of osteoporosis and lose muscle bulk early in the course of the disease. Basal metabolic rate is increased in HF, but general malnutrition may play a part in the development of cachexia, particularly in an elderly population. There is evidence for a possible role for micronutrient deficiency in HF. Selective deficiency of selenium, calcium and thiamine can directly lead to the HF syndrome. Other nutrients, particularly vitamins C and E and beta-carotene, are antioxidants and may have a protective effect on the vasculature. Vitamins B6, B12 and folate all tend to reduce levels of homocysteine, which is associated with increased oxidative stress. Carnitine, co-enzyme Q10 and creatine supplementation have resulted in improved exercise capacity in patients with HF in some studies. In this article, we review the relation between micronutrients and HF. Chronic HF is characterized by high mortality and morbidity, and research effort has centered on pharmacological management, with the successful introduction of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists into routine practice. There is sufficient evidence to support a large-scale trial of dietary micronutrient supplementation in HF.

Application of Tissue Doppler Imaging in Cardiology

Tissue Doppler imaging (TDI) is a new echocardiographic technique employing the Doppler principle to measure the velocity of myocardial segments and other cardiac structures. It is well suited for the measurement of long-axis ventricular function. Impairment of longitudinal myocardial fiber motion is a sensitive marker of early myocardial dysfunction and ischaemia, and TDI might therefore become an important tool in routine echocardiography. The technique allows truly quantitative measurement of regional myocardial function both at rest and during stress echocardiography. TDI has great potential in the diagnosis of diastolic left ventricular dysfunction, overcoming the load-dependence of conventional Doppler techniques. Right ventricular function, intracardiac and pulmonary artery pressures, transplant rejection and intraventricular dyssynchrony can also be assessed. This article reviews the current and evolving applications of TDI in cardiology.

Chronic heart failure, chronotropic incompetence, and the effects of β blockade

Objective: To establish the prevalence of chronotropic incompetence in a cohort of patients with chronic heart failure (CHF) taking modern medications for heart failure, and whether this affected exercise capacity and predicted prognosis. Methods: Heart rate response to exercise was examined in 237 patients with CHF in sinus rhythm, who were compared with 118 control volunteers. The percentage of maximum age predicted peak heart rate (%Max-PPHR) and percentage heart rate reserve (%HRR) were calculated, with a cut off of < 80% as the definition of chronotropic incompetence for both. Patients were followed up for an average (SD) of 2.8 (9) years. Mortality was related to peak oxygen consumption (pVo2), and the presence or absence of chronotropic incompetence. Results: %Max-PPHR < 80% identified 103 (43%) and %HRR < 80% identified 170 patients (72%) as having chronotropic incompetence. Chronotropic incompetence was more common in patients taking β blockers than in those not taking β blockers as assessed by both methods (80 (49%) v 23 (32%) by %Max-PPHR and 123 (75%) v 47 (64%) by %HRR, respectively). Patients with chronotropic incompetence by either method had a lower pVo2 than those without. These differences remained significant for both patients taking and not taking a β blocker. %HRR, Max-PPHR%, and HRR were related to New York Heart Association class and correlated with pVo2. There was no difference in the slopes relating heart rate to pVo2 between patients with and those without chronotropic incompetence (6.1 (1.7) v 5.1 (1.8), p  =  0.34). During an average 2.8 year follow up 40 patients (17%) died. In Cox proportional hazard models, pVo2 was the most powerful predictor of survival and neither measure of chronotropic incompetence independently predicted outcome. Conclusions: pVo2 is a powerful marker of prognosis for patients with CHF whether they are taking β blockers or not. A low heart rate response to exercise in patients with CHF correlates with worse exercise tolerance but is unlikely to contribute to exercise impairment.

Color tissue Doppler-derived long-axis left ventricular function in heart failure with preserved global systolic function.

The mechanism causing symptoms and signs of heart failure (HF) in patients with preserved global left ventricular (LV) systolic function remains poorly defined. Conventionally, LV diastolic dysfunction is implicated as a major factor responsible for the clinical syndrome of HF in these patients, provided that valvular heart disease, cor pulmonale, volume overload conditions, and noncardiac causes of symptoms are excluded. 1 Early LV functional abnormalities can be detected using analysis of its longitudinal function 2,3 by M-mode echocardiography, magnetic resonance imaging, or tissue Doppler imaging. In the present study we investigated long-axis LV function in patients with symptoms of HF and preserved global LV systolic function using color tissue Doppler imaging. ••• From 220 consecutive attendees (14 women and 206 men, aged 68 12 years) referred to a HF clinic we identified 44 patients with signs and symptoms of compensated HF (New York Heart Association functional class II and III) and preserved global LV systolic function according to the criteria proposed by the European Study Group on Diastolic Heart Failure (LV ejection fraction 45% and LV end-diastolic diameter index 3.2 cm/m 2 or LV end-diastolic volume index 102 ml/m 2 ). 4 Twenty-five patients had ischemic heart disease (16 with previous myocardial infarction), 16 patients had a history of hypertension, and 3 patients were previously diagnosed with idiopathic dilated cardiomyopathy. All patients had been receiving diuretics and angiotensin-converting enzyme inhibitors or angiotensin II antagonists at optimal doses and had been stable for the preceding 3 months. We performed basic spirometry on all patients to exclude pulmonary disease. The control group was composed of 44 subjects (16 women and 28 men, aged 68 11 years) with no known cardiovascular disease. Each subject underwent full echocardiographic examination including color-coded tissue Doppler imaging using commercially available equipment (GE Vingmed Vivid Five scanner, Horten, Norway) equipped with a 2.5-MHz phased-array transducer. The parasternal long-axis view was used to derive left atrial dimension at end-systole. Measurements of LV end-diastolic volumes and end-systolic volumes were performed using the modified Simpson’ s rule and LV ejection fraction was calculated. Early filling (E) and atrial filling (A) peak velocities, E/A ratio, deceleration time of early filling, and isovolumic relaxation time were measured from transmitral flow, and systolic (S), diastolic (D), and atrial reversal peak velocities were derived from pulmonary venous flow using pulsed Doppler. In color tissue Doppler mode, images were obtained in 3 apical views (4-chamber, 2-chamber, and apical long-axis), and stored digitally on magnetic optical disks. The coded data were reviewed off-line with a software analysis system (Echopac 6.3, GE Vingmed). Mitral annular systolic velocities (S m), ignoring the

Clinical trials update: OPTIME‐CHF, PRAISE‐2, ALL‐HAT

This is a summary of reports of presentation made at the American College of Cardiology 49th Scientific Sessions, Anaheim, 12–15 March 2000. Studies with a particular interest for heart failure physicians have been reviewed. OPTIME‐CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. OPTIME‐CHF was a randomised‐controlled trial comparing a 48‐h infusion of Milrinone or standard therapy in 951 patients recruited over a 2‐year period. Patients were excluded if the investigator believed their clinical condition mandated inotropic therapy. Patients were randomised within 48 h of admission for an acute exacerbation of chronic heart failure to receive Milrinone or placebo infision for 48 h. Of the patients 43% were diabetics, 70% were receiving an angiotensin converting enzyme inhibitor, 25% were already on a beta‐Blocker, and 34% had atrial fibrillation. There was no significant difference between the two groups in length of hospital stay during the index admission, subsequent readmissions and days in hospital over the following 60 days. Subjective clinical assessment scores were also no different. There was an average admission rate over the next year of one per patient in both groups. However, there was a significant increase in the incidence of sustained hypotension in the Milrinone group, which accounted for all of the increased adverse event rates for the active therapy. The 60‐day mortality was 10% in both groups. This and previous trials of the oral formulation of Milrinone have now clearly demonstrated a lack of benefit with Milrinone in either during acute exacerbations of or in stable severe chronic heart failure [Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral Milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468–1475.]. Medium sized studies of Milrinone in patients with milder severities of heart failure also suggested an adverse impact on prognosis in the presence or absence of digoxin [DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral Milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677–683.]. Whether Milrinone even has a role for the management of a haemodyamic crisis requiring inotropic therapy must also be questioned.

Non-invasive Vagus Nerve Stimulation in Healthy Humans Reduces Sympathetic Nerve Activity

BACKGROUND Vagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimers disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of the mechanisms involved. OBJECTIVE We investigated a non-invasive method of VNS through electrical stimulation of the auricular branch of the vagus nerve distributed to the skin of the ear--transcutaneous VNS (tVNS) and measured the autonomic effects. METHODS The effects of tVNS parameters on autonomic function in 48 healthy participants were investigated using heart rate variability (HRV) and microneurography. tVNS was performed using a transcutaneous electrical nerve stimulation (TENS) machine and modified surface electrodes. Participants visited the laboratory once and received either active (200 μs, 30 Hz; n = 34) or sham (n = 14) stimulation. RESULTS Active tVNS significantly increased HRV in healthy participants (P = 0.026) indicating a shift in cardiac autonomic function toward parasympathetic predominance. Microneurographic recordings revealed a significant decrease in frequency (P = 0.0001) and incidence (P = 0.0002) of muscle sympathetic nerve activity during tVNS. CONCLUSION tVNS can increase HRV and reduce sympathetic nerve outflow, which is desirable in conditions characterized by enhanced sympathetic nerve activity, such as heart failure. tVNS can therefore influence human physiology and provide a simple and inexpensive alternative to invasive VNS.

The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades

Cardiac resynchronization therapy (CRT) is an effective treatment for a subset of patients with chronic heart failure. Data on the benefit of CRT in heart failure patients with previous right ventricular pacemakers or standard defibrillators are sparse.

Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology

Background: It is unclear whether diabetes mellitus (DM) is an adverse prognostic factor in chronic heart failure (CHF) of ischaemic and non-ischaemic aetiology managed with contemporary evidence-based care. Methods: In total, 1091 outpatients with CHF with reduced ejection fraction were prospectively observed for a mean of 960 days. Total and cardiovascular mortality was quantified after accounting for potential confounders. Results: In total, 25.7% of patients had DM; this group was more likely to have CHF of ischaemic aetiology and was more symptomatic. Patients with DM received comparable medical- and device-based therapies, except for greater doses of loop diuretic. DM was associated with approximately doubled crude and adjusted risk of total and cardiovascular mortality. The association of diabetes with these outcomes in patients with ischaemic and non-ischaemic cardiomyopathies was of similar magnitude. Conclusions: In spite of advances in the management of CHF, DM remains a major adverse prognostic feature, irrespective of ischaemic/non-ischaemic aetiology.

Nutritional abnormalities contributing to cachexia in chronic illness

Cachexia is a common consequence of chronic illness. The nutritional abnormalities contributing to the clinical picture are often a composite of reduced appetite, dietary factors including protein, energy and micronutrient intake, malabsorption and increased consumption or loss of nutrients. In this article, using chronic heart failure as an example, we have reviewed the potential influences of chronic disease on each of these and how they might lead to the relentless progression of wasting and the poor prognosis associated with it.