Pierpaolo Pellicori

IVC Diameter in Patients With Chronic Heart Failure : Relationships and Prognostic Significance

OBJECTIVES The aim of this study was to assess the relation between inferior vena cava (IVC) diameter, clinical variables, and outcome in patients with chronic heart failure (HF). BACKGROUND The IVC distends as right atrial pressure rises. Therefore it might represent an index of HF severity independent of left ventricular ejection fraction (LVEF). The relation between IVC diameter and other clinical variables and its prognostic significance in patients with HF has not been explored. METHODS Outpatients attending a community HF service between 2008 and 2010 were enrolled. Heart failure was defined as the presence of relevant symptoms and signs and objective evidence of cardiac dysfunction: either LVEF <45% or the combination of both left atrial dilation (≥4 cm) and raised amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml. Patients were followed for a median of 567 (interquartile range: 413 to 736) days. The primary composite endpoint was cardiovascular death and HF hospitalization. RESULTS Among the 693 patients enrolled, median age was 73 years, 33% were women, and 568 had HF. Patients with HF in the highest tertile of IVC diameter were older; had lower body mass index; were more likely to have atrial fibrillation and to be treated with diuretics; and had larger left atrial volumes, higher pulmonary pressures, and less negative values for global longitudinal strain. The LVEF and systolic blood pressure were similar across tertiles of IVC diameter. The IVC diameter and log [NT-proBNP] were correlated (r = 0.55, p < 0.001). During follow-up, 158 patients reached a primary endpoint. In a multivariable Cox regression model, including NT-proBNP, only increasing IVC diameter, urea, and the trans-tricuspid systolic gradient independently predicted a poor outcome. Neither global longitudinal strain nor LVEF were adverse predictors. CONCLUSIONS In patients with chronic HF with or without a reduced LVEF, increasing IVC diameter identifies patients with an adverse outcome.

Renal dysfunction in acute and chronic heart failure: prevalence, incidence and prognosis

Most patients with heart failure have mild or moderate renal dysfunction. This reflects the combined impact of chronic renal parenchymal disease, renal artery disease, renal congestion and hypoperfusion, neuroendocrine and cytokine activation and the effects of treatments for heart failure. Remarkably, with good treatment, the average annual rate of decline in renal function is similar in patients with chronic heart failure and healthy people of a similar age. Urea appears to be a stronger marker of an adverse prognosis than creatinine-based measures of renal function. Recent evidence suggests that minor, transient increases in creatinine in the setting of acute heart failure are not prognostically important but persistent deterioration does indicate a higher mortality. The poor prognosis of patients with worsening renal function ensures that few require renal dialysis but this may change as methods to prevent sudden death improve and new ways are found to control fluid congestion. Reversing renal dysfunction and stopping its progression remain important targets for treatment of heart failure.

Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value

BACKGROUND Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. METHODS Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). RESULTS Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. CONCLUSIONS In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction.

Cardiac dysfunction in cirrhosis is not associated with the severity of liver disease

BACKGROUND Cirrhotic cardiomiopathy is described as the presence of cardiac dysfunction in cirrhotic patients. The aim of the study was to investigate factors associated with cardiac dysfunction in cirrhotic patients. PATIENTS AND METHODS Seventy-four cirrhotic patients and twenty-six controls performed a conventional echocardiography and Tissue Doppler Imaging (TDI) for systolic and diastolic function. Results were analyzed by using the Guidelines of American Society of Echocardiography. RESULTS In patients with cirrhosis, left ventricular end-diastolic diameter was increased (p<0.001) , peak systolic velocities were decreased (11.3±2.7 vs 13.9±1.4cm/s; p<0.001) and left atrial volumes were increased (32.7±8.3 vs 24±8.5ml, p<0.001) as well as cardiac mass (90.6±23 vs 70.5±22g/m(2), p<0.001). Forty-seven cirrhotic patients (64%) showed diastolic dysfunction at rest: grade I in 37 and grade II in 10 patients. Systolic and/or diastolic dysfunction were not influenced by a more severe liver impairment. Diastolic dysfunction was more prevalent in patients with ascites vs those without (77% vs 56%; p=0.04). CONCLUSION A mild diastolic dysfunction at rest is frequent in cirrhotic patients but cardiac load conditions are confounding factors in this diagnosis. We did not identify an association between severity of liver disease and cardiac dysfunction.

Defining Diastolic Heart Failure and Identifying Effective Therapies

In this issue of JAMA, Edelmann and colleagues1 report the results of the first substantial randomized, placebo-controlled study investigating the effects of a mineralocorticoid antagonist (MRA), spironolactone, on cardiac function and exercise capacity in patients diagnosed as having heart failure with preserved ejection fraction (HFpEF). The Aldo-DHF trial included 422 patients (mean age, 67 years; 52% women) with chronic, stable symptoms attributed to heart failure, a left ventricular ejection fraction (LVEF) of at least 50%, echocardiographic evidence of LV diastolic dysfunction or atrial fibrillation, and a peak exercise oxygen consumption of 25 mL/kg/min or less during bicycle exercise. Most patients were receiving treatment for hypertension, including thiazide diuretics.1 After 12 months, patients assigned to spironolactone had lower cardiac filling pressures and LV mass, but this did not translate into improved symptoms or exercise capacity. Spironolactone was associated with a slight decline in glomerular filtration and hemoglobin concentration but not with marked hyperkalemia. Only 1 patient died during follow-up.

Clinical trials update from the American Heart Association Meeting 2010: EMPHASIS-HF, RAFT, TIM-HF, Tele-HF, ASCEND-HF, ROCKET-AF, and PROTECT

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Chicago in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In patients with mild heart failure (HF), EMPHASIS‐HF showed that the addition of eplerenone to standard therapy was well tolerated and reduced both the risk of death and hospitalization. The addition of cardiac resynchronization therapy to implantable cardioverter defibrillator (ICD) therapy reduced the incidence of all‐cause mortality and HF hospitalizations in patients with NYHA class II–III HF compared with ICD alone in RAFT. Telemonitoring failed to improve outcome compared with a high standard of conventional care in patients with chronic HF (TIM‐HF study) and a telephone‐based interactive voice response system failed to improve outcome in patients recently hospitalized for HF (Tele‐HF study). ASCEND‐HF suggested that nesiritide was ineffective but safe in patients with acute decompensated HF. ROCKET‐AF suggests that the factor‐Xa inhibitor rivaroxaban may be as effective as warfarin in patients with atrial fibrillation. The PROTECT study provided more data to suggest that amino‐terminal B‐type natriuretic peptide guided therapy may be beneficial in patients with left ventricular systolic dysfunction.

Prevalence and Outcomes of Anemia and Hematinic Deficiencies in Patients With Chronic Heart Failure

IMPORTANCE Detailed information on the prevalence, associations, and consequences of anemia and iron deficiency in epidemiologically representative outpatients with chronic heart failure (HF) is lacking. OBJECTIVE To investigate the epidemiology of anemia and iron deficiency in a broad range of patients referred to a cardiology clinic with suspected HF. DESIGN, SETTING, AND PARTICIPANTS We collected clinical data, including hemoglobin, serum iron, transferrin saturation, and serum ferritin concentrations, on consecutive patients referred with suspected HF to a single outpatient clinic serving a local community from January 1, 2001, through December 31, 2010. Follow-up data were censored on December 13, 2011. Patients underwent phenotyping by echocardiography and plasma N-terminal pro-brain natriuretic peptide measurement and were followed for up to 10 years. MAIN OUTCOME MEASURES Prevalences of anemia and iron deficiency and their interrelationship, all-cause mortality, and cardiovascular mortality. RESULTS Of 4456 patients enrolled in the study, the median (interquartile range) age was 73 (65-79) years, 2696 (60.5%) were men, and 1791 (40.2%) had left ventricular systolic dysfunction (LVSD). Of those without LVSD, plasma N-terminal pro-brain natriuretic peptide concentration was greater than 400 pg/mL in 1172 (26.3%), less than 400 pg/mL in 841 (18.9%), and not measured in 652 (14.6%). Overall, 1237 patients (27.8%) had anemia, with a higher prevalence (987 [33.3%]) in patients who met the criteria for HF with or without LVSD. Depending on the definition applied, iron deficiency was present in 270 (43.2%) to 425 (68.0%) of patients with and 260 (14.7%) to 624 (35.3%) of patients without anemia. Lower hemoglobin (hazard ratio 0.92; 95% CI, 0.89-0.95; P < .001) and serum iron (hazard ratio 0.98; 95% CI, 0.97-0.99; P = .007) concentrations were independently associated with higher all-cause and cardiovascular mortality in multivariable analyses. CONCLUSIONS AND RELEVANCE Anemia is common in patients with HF and often associated with iron deficiency. Both anemia and iron deficiency are associated with an increase in all-cause and cardiovascular mortality and might both be therapeutic targets in this population.

A Meta-Analysis of the Therapeutic Effects of Glucagon-Like Peptide-1 Agonist in Heart Failure

We conducted a meta-analysis of the existing literature of the therapeutic effects of using GLP-1 agonists to improve the metabolism of the failing heart. Animal studies showed significant improvement in markers of cardiac function, such as left ventricular ejection fraction (LVEF), with regular GLP-1 agonist infusions. In clinical trials, the potential effects of GLP-1 agonists in improving cardiac function were modest: LVEF improved by 4.4% compared to placebo (95% C.I 1.36–7.44, P = 0.005). However, BNP levels were not significantly altered by GLP-1 agonists in heart failure. In two trials, a modest increase in heart rate by up to 7 beats per minute was noted, but meta-analysis demonstrated this was not significant statistically. The small number of studies plus variation in the concentration and length of the regime between the trials would limit our conclusions, even though statistically, heterogeneity chi-squared tests did not reveal any significant heterogeneity in the endpoints tested. Moreover, studies in non-diabetics with heart failure yielded conflicting results. In conclusion, the use of GLP-1 agonists has at best a modest effect on ejection fraction improvement in heart failure, but there was no significant improvement in BNP levels in the meta-analysis.

Telemonitoring in heart failure: Big Brother watching over you

Abstract Heart failure (HF) is a leading cause of hospitalisations in older people. Several strategies, supported by novel technologies, are now available to monitor patients’ health from a distance. Although studies have suggested that remote monitoring may reduce HF hospitalisations and mortality, the study of different patient populations, the use of different monitoring technologies and the use of different endpoints limit the generalisability of the results of the clinical trials reported, so far. In this review, we discuss the existing home monitoring modalities, relevant trials and focus on future directions for telemonitoring.

Clinical Trials in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction

There is no robust evidence that any treatment can modify the natural history of patients with heart failure and preserved left ventricular ejection fraction (HFpEF), although most agree that diuretics can control congestion and improve symptoms. HFpEF is often complicated by systemic and pulmonary hypertension, atrial fibrillation, obesity, chronic lung and kidney disease, lack of physical fitness, and old age that can complicate both diagnosis and management. Further trials should phenotype patients precisely and create better definitions of HFpEF based on biomarkers.