Henry J. Dargie

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaborati

Authors/Task Force Members: John J.V. McMurray (Chairperson) (UK)*, Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Angelo Auricchio (Switzerland), Michael Bohm (Germany), Kenneth Dickstein (Norway), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Cândida Fonseca (Portugal), Miguel Angel Gomez-Sanchez (Spain), Tiny Jaarsma (Sweden), Lars Kober (Denmark), Gregory Y.H. Lip (UK), Aldo Pietro Maggioni (Italy), Alexander Parkhomenko (Ukraine), Burkert M. Pieske (Austria), Bogdan A. Popescu (Romania), Per K. Ronnevik (Norway), Frans H. Rutten (The Netherlands), Juerg Schwitter (Switzerland), Petar Seferovic (Serbia), Janina Stepinska (Poland), Pedro T. Trindade (Switzerland), Adriaan A. Voors (The Netherlands), Faiez Zannad (France), Andreas Zeiher (Germany).

Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population

BACKGROUND In most previous epidemiological studies on the prevalence of chronic heart failure (CHF) the disorder has been defined on clinical criteria. In a cross-sectional survey of 2000 men and women aged 25-74, randomly sampled from one geographical area, we assessed left-ventricular systolic function by echocardiography. METHODS 1640 (83%) of those invited took part. They completed a questionnaire on current medication, history, and symptoms of breathlessness. Blood pressure was measured and electrocardiography (ECG) and echocardiography were done. Left-ventricular ejection fraction was measurable in 1467 (89.5%) participants by the biplane Simpsons rate method. FINDINGS The mean left-ventricular ejection fraction was 47.3%. The prevalence of definite left-ventricular systolic dysfunction (defined as a left-ventricular ejection fraction < or = 30%) was 2.9% overall (43 participants); it increased with age and was higher in men than in women (4.0 vs 2.0%). The left-ventricular systolic dysfunction was symptomatic in 1.5% of participants and asymptomatic in 1.4%, 83% of participants with left-ventricular systolic dysfunction had evidence of ischaemic heart disease (IHD) from history or ECG criteria compared with 21% of those without this abnormality (p < 0.001). Hypertension was also more common in those with left-ventricular systolic dysfunction (72 vs 38%, p < 0.001), but there was no difference between those with and without left-ventricular systolic dysfunction in the rate of hypertension without IHD. INTERPRETATION Left-ventricular systolic dysfunction was at least twice as common as symptomatic heart failure defined by clinical criteria. The main risk factors are IHD and hypertension in the presence of IHD; screening of such high-risk groups for left-ventricular systolic dysfunction should be considered.

Ventricular Arrhythmias in Patients with Hypertensive Left Ventricular Hypertrophy

In patients with hypertension, a pattern of left ventricular hypertrophy on the electrocardiogram is associated with a risk of sudden death in excess of the risk attributable to hypertension alone. We therefore investigated the frequency of complex ventricular arrhythmias by means of 48-hour ambulatory electrocardiographic monitoring in 100 treated hypertensive patients, of whom 50 had electrocardiographic evidence of left ventricular hypertrophy and 50 did not, and in 50 normotensive controls. The groups were matched for age, sex, and smoking habits, and the two hypertensive groups were matched for blood-pressure levels before and after antihypertensive therapy. Nonsustained ventricular tachycardia, defined as greater than or equal to 3 complexes at a rate greater than or equal to 120 beats per minute, occurred in 14 (28 percent) of the 50 patients with an electrocardiographic pattern of left ventricular hypertrophy, in 4 (8 percent) of the 50 patients without hypertrophy (P less than 0.05), and in 1 (2 percent) of the control subjects. Eight of the 50 patients (16 percent) with hypertrophy had episodes of nonsustained ventricular tachycardia longer than 5 complexes, whereas no patients without hypertrophy and no controls had such episodes. The group with nonsustained ventricular tachycardia was characterized by a high left ventricular mass on echocardiography and a high prevalence of ST-T abnormalities on electrocardiography. Ventricular tachycardia was not closely related to blood-pressure levels, nor was it associated with diuretic therapy or hypokalemia. The clinical importance of these arrhythmias is uncertain. Nevertheless, our data suggest that complex ventricular arrhythmias occur commonly in hypertensive patients with left ventricular hypertrophy and may contribute to the higher incidence of sudden death in these patients.

Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial

Background —&bgr;-Blockade–induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated. Methods and Results —In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to &bgr;-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, P <0.001) but not in patients with atrial fibrillation (relative risk 1.16, P =NS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening. Conclusions —BHR and HRC are significantly related to prognosis in heart failure. &bgr;-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.

Novel Role for the Potent Endogenous Inotrope Apelin in Human Cardiac Dysfunction

Background—Apelin is among the most potent stimulators of cardiac contractility known. However, no physiological or pathological role for apelin–angiotensin receptor-like 1 (APJ) signaling has ever been described. Methods and Results—We performed transcriptional profiling using a spotted cDNA microarray with 12 814 unique clones on paired samples of left ventricle obtained before and after placement of a left ventricular assist device in 11 patients. The significance analysis of microarrays and a novel rank consistency score designed to exploit the paired structure of the data confirmed that natriuretic peptides were among the most significantly downregulated genes after offloading. The most significantly upregulated gene was the G-protein–coupled receptor APJ, the specific receptor for apelin. We demonstrate here using immunoassay and immunohistochemical techniques that apelin is localized primarily in the endothelium of the coronary arteries and is found at a higher concentration in cardiac tissue after mechanical offloading. These findings imply an important paracrine signaling pathway in the heart. We additionally extend the clinical significance of this work by reporting for the first time circulating human apelin levels and demonstrating increases in the plasma level of apelin in patients with left ventricular dysfunction. Conclusions—The apelin-APJ signaling pathway emerges as an important novel mediator of cardiovascular control.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology.

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition.

Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: Randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy

BACKGROUND Most patients with chronic heart failure (CHF) receive the same dose of angiotensin-converting enzyme (ACE) inhibitors because there is currently no measure of treatment efficacy. We sought to determine whether titration of vasodilator therapy according to plasma brain natriuretic peptide (BNP) concentration may be of value in the individual optimization of vasodilator therapy in CHF. METHODS AND RESULTS Twenty patients with mild to moderate CHF receiving stable conventional therapy including an ACE inhibitor were randomly assigned to titration of ACE inhibitor dosage according to serial measurement of plasma BNP concentration (BNP group) or optimal empirical ACE inhibitor therapy (clinical group) for 8 weeks. Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the duration of the study and a significantly greater suppression when compared with empiric therapy after 4 weeks [-42.1% (-58.2, -19.7) vs -12.0% (-31.8, 13.8), P =.03]. Both treatment strategies were well tolerated and associated with favorable neurohormonal and hemodynamic effects; however, in comparison between groups, mean heart rate fell (P =.02) and plasma renin activity rose (P =.03) in the BNP group when compared with the clinical group. CONCLUSIONS Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF. Furthermore, titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate when compared with empiric therapy.

Diagnosis and management of heart failure.

#### Summary points Doctors diagnose heart failure when patients whom they suspect of having heart disease develop fatigue, dyspnoea, or oedema. By these standards, this is a terminal condition because in severe cases its annual mortality may exceed 60 %1 Even in so called mild cases detected in community screening programmes such as the Framingham study the five year mortality approached 50 %.2 These survival rates are worse than for many of the common forms of cancer, emphasising that heart failure is indeed a malignant condition. Heart failure also imposes a heavy burden of symptoms. In studies of the major chronic illnesses such as diabetes, arthritis, and hypertension, heart failure had the greatest negative impact on quality of life, and not just slightly so.3,4 The high morbidity is also reflected in the number of hospital admissions for heart failure, about 120 000 cases each year in the United Kingdom.5,6 These represent 5% of all adult medical and geriatric admissions and are about the same as the number of admissions for acute myocardial infarction.7 Heart failure is a serious public health problem, with a prevalence in the United Kingdom, Scandinavia, and the …

The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: Results of the UK natriuretic peptide study

To determine the diagnostic accuracy of the measurement of plasma B‐type natriuretic peptide (BNP) and N‐terminal pro‐BNP (NTproBNP) in patients referred by their general practitioners (GPs) with symptoms suggestive of heart failure. Additionally, to compare the diagnostic accuracy of the resting 12‐lead electrocardiogram (ECG) with that of the peptides.

Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction.

OBJECTIVES This study sought to assess, for the first time, the relationship between serum concentrations of the soluble interleukin-1 receptor family member ST2 (sST2) and serial change in left ventricular (LV) function after acute myocardial infarction (AMI). BACKGROUND Serum sST2 levels are elevated early after AMI and are associated with lower pre-discharge LV ejection fraction and adverse cardiovascular outcomes. METHODS The sST2 levels were measured in 100 patients (mean age 58.9 +/- 12.0 years; 77% male), admitted with AMI with resultant LV systolic dysfunction, at baseline and at 12 and 24 weeks. Patients underwent cardiac magnetic resonance imaging and measurement of N-terminal pro-brain natriuretic peptide, norepinephrine, and aldosterone at each time point. RESULTS Median sST2 decreased from 263.3 pg/ml at baseline to 140.0 pg/ml at 24 weeks (p < 0.001). Serum sST2 correlated significantly with LV ejection fraction at baseline (r = -0.30, p = 0.002) and 24 weeks (r = -0.23, p = 0.026); change in sST2 correlated with change in LV end-diastolic volume index (r = -0.24, p = 0.023). Level of sST2 was positively associated with infarct volume index at baseline (r = 0.26, p = 0.005) and 24 weeks (r = 0.22, p = 0.037), and with change in infarct volume index (r = -0.28, p = 0.001). Level of sST2 was significantly higher in patients with greater infarct transmurality and endocardial extent, and in the presence of microvascular obstruction. Level of sST2 correlated significantly with norepinephrine and aldosterone, but not with N-terminal pro-brain natriuretic peptide. CONCLUSIONS Measurement of sST2 early after AMI assists in the prediction of medium-term LV functional recovery. Novel relationships were observed between sST2, infarct magnitude/evolution, and aldosterone. Serum sST2 may be of pathophysiological importance in ventricular and infarct remodeling after AMI. (Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack; NCT00132093).