The prevalence and clinical associations of ultrasound measures of congestion in patients at risk of developing heart failure.

AIMS: Congestion is a cardinal feature of untreated heart failure (HF) and might be detected by ultrasound (US) before overt clinical signs appear. METHODS AND RESULTS: We investigated the prevalence and clinical associations of subclinical congestion in 238 patients with at least one clinical risk factor for HF (diabetes, ischaemic heart disease, or hypertension) using three US variables: (i) inferior vena cava (IVC) diameter; (ii) jugular vein distensibility (JVD) ratio (the ratio of the jugular vein diameter during the Valsalva manoeuvre to that at rest); (iii) the number of B-lines from a 28-point lung US. US congestion was defined as IVC diameter > 2.0 cm, JVD ratio < 4.0 or B-lines count > 14. The prevalence of subclinical congestion (defined as at least one positive US marker of congestion) was 30% (13% by IVC diameter, 9% by JVD ratio and 13% by B-line quantification). Compared to patients with no congestion on US, those with at least one marker had larger left atria and higher plasma concentrations of natriuretic peptides. Patients with raised plasma N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide had a lower JVD ratio (7.69 vs. 8.80; P = 0.05) and more often had at least one lung B-line (74% vs. 63%; P = 0.05). However, plasma natriuretic peptide concentrations were more closely related to left atrial volume than other US measures of congestion. CONCLUSIONS: Subclinical evidence of congestion by US is common in patients with clinical risk factors for HF. Whether these measurements provide additional value for predicting the development of HF and its prevention deserves consideration.

A comparison of non-invasive methods of measuring body composition in patients with heart failure: a report from SICA-HF.

BACKGROUND: Cachexia is common in patients with chronic heart failure and is associated with poor prognosis. How best to measure body composition is not clear. METHODS AND RESULTS: We characterized body composition in 120 patients with chronic heart failure: mean (SD) age 70 (10) years, left ventricular ejection fraction 44 (10) %, and median (Q1-Q3) N-terminal pro B-type natriuretic peptide 845 (355-1368) ng/L. We measured body composition using dual-energy X-ray absorptiometry (DEXA) and a multi-frequency bioelectrical impedance analysis (BIA) device (Tanita BIA MC-180MA). Mean (SD) fat mass (FM) was 27.2 (11.7) kg by BIA and 32.3 (12.2) kg by DEXA (mean difference -5.1 kg, 95% limits of agreement: -11.7, 1.5; 4% of values outside limit of agreement); mean (SD) lean mass (LM) was 56.6 (10.9) kg by BIA and 51.1 (9.9) kg by DEXA (mean difference 5.5 kg, 95% limits of agreement: -1.3, 12.3; 6% of values outside limit of agreement); and mean (SD) bone mass (BM) was 3.0 (0.5) kg by BIA and 2.8 (0.6) kg by DEXA (mean difference 0.2 kg, 95% limits of agreement: -0.5, 0.8; 5% of values outside limit of agreement). There was a close correlation between DEXA and BIA for both LM and FM (LM: r = 0.95, P < 0.001; FM: r = 0.96, P < 0.001) but less so for BM (r = 0.84, P < 0.001). Both DEXA and BIA body composition measurements correlated well with other measures of body size (body mass index, hip circumference, and waist circumference). CONCLUSIONS: There are differences in the measurements of FM, LM, and BM between the two techniques, which should not be used interchangeably.

Clinical and prognostic association of total atrial conduction time in patients with heart failure: a report from Studies Investigating Co-morbidities Aggravating Heart Failure.

BACKGROUND: The total atrial conduction time can be measured as the time from the onset of the P wave on the ECG to the peak of the A wave recorded at the mitral annulus using tissue Doppler imaging (A'; P-A'TDI); when prolonged, it might predict incident atrial fibrillation. METHODS: We measured P-A'TDI in outpatients with heart failure and sinus rhythm enrolled in the SICA-HF programme. RESULTS: P-A'TDI measured at the lateral mitral annulus was longer in patients with HF with reduced [LVEF<50%, N = 141; 126 (112-146) ms; P = 0.005] or preserved left ventricular ejection fraction [LVEF>50% and NT-proBNP > 125 ng/l, N = 71; 128 (108-145) ms; P = 0.026] compared to controls [N = 117; 120 (106-135) ms]. Increasing age, left atrial volume and PR interval were independently associated with prolonged P-A'TDI. During a median follow-up of 1251 (956-1602) days, 73 patients with heart failure died (N = 42) or developed atrial fibrillation (N = 31). In univariable analysis, P-A'TDI was associated with an increased risk of the composite outcome of death or atrial fibrillation, but only increasing log [NT-proBNP], age and more severe symptoms (NYHA III vs. I/II) were independently related to this outcome. Patients in whom both P-A'TDI and left atrial volume were above the median (127 ms and 64 ml, respectively) had the highest incidence of atrial fibrillation (hazard ratio 6.61, 95% CI 2.27-19.31; P < 0.001 compared with those with both P-A'TDI and LA volume below the median). CONCLUSION: Measuring P-A'TDI interval identifies patients with chronic heart failure at higher risk of dying or developing atrial fibrillation during follow-up.

Correction to: Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study.

The original article [1] contains an error in the presentation of Table 4.

Prevalence, pattern and clinical relevance of ultrasound indices of congestion in outpatients with heart failure.

AIMS: Even if treatment controls symptoms, patients with heart failure may still be congested. We aimed at assessing the prevalence and clinical relevance of congestion in outpatients with chronic heart failure. METHODS AND RESULTS: We recorded clinical and ultrasound [lung B-lines; inferior vena cava (IVC) diameter; internal jugular vein diameter before and after a Valsalva manoeuvre (JVD ratio)] features of congestion in heart failure patients during a routine check-up. Of 342 patients who attended, predominantly in New York Heart Association class I or II (n = 257; 75%), 242 (71%) had at least one feature of congestion, either clinical (n = 139; 41%) or by ultrasound (n = 199; 58%). Amongst patients (n = 203, 59%) clinically free of congestion, 31 (15%) had ≥ 14 B-lines, 57 (29%) had a dilated IVC (> 2.0 cm), 38 (20%) had an abnormal JVD ratio (< 4), 87 (43%) had at least one of these, and 27 (13%) had two or more. During a median follow-up of 234 (interquartile range 136-351) days, 60 patients (18%) died or were hospitalized for heart failure. In univariable analysis, each clinical and ultrasound measure of congestion was associated with increased risk but, in multivariable models, only higher N-terminal pro-B-type natriuretic peptide and IVC, and lower JVD ratio, were associated with the composite outcome. CONCLUSIONS: Many patients with chronic heart failure with few symptoms have objective evidence of congestion and this is associated with an adverse prognosis. Whether using these measures of congestion to guide management improves outcomes requires investigation.

Warm water immersion in patients with chronic heart failure: a pilot study : Shah immerse: HF.

BACKGROUND: Patients with chronic conditions, such as heart failure, swim regularly and most rehabilitation exercises are conducted in warm hydrotherapy pools. However, little is known about the acute effects of warm water immersion (WWI) on cardiac haemodynamics in patients with chronic heart failure (CHF). METHODS: Seventeen patients with CHF (NYHA I and II; mean age 67 years, 88% male, mean left ventricular ejection fraction 33%) and 10 age-matched normal subjects were immersed up to the neck in a hydrotherapy pool (33-35 °C). Cardiac haemodynamics were measured non-invasively, and echocardiography was performed at baseline, during WWI, 3 min after kicking in the supine position and after emerging. RESULTS: In patients with CHF, compared to baseline, WWI immediately increased stroke volume (SV, mean ± standard deviation; from 65 ± 21 to 82 ± 22 mL, p < 0.001), cardiac output (CO, from 4.4 ± 1.4 to 5.7 ± 1.6 L/min, p < 0.001) and cardiac index (CI, from 2.3 ± 0.6 to 2.9 ± 0.70 L/min/m², p < 0.001) with decreased systemic vascular resistance (from 1881 ± 582 to 1258 ± 332 dynes/s/cm5, p < 0.001) and systolic blood pressure (132 ± 21 to 115 ± 23 mmHg, p < 0.001). The haemodynamic changes persisted for 15 min of WWI. In normal subjects, compared to baseline, WWI increased SV (from 68 ± 11 to 80 ± 18 mL, p < 0.001), CO (from 5.1 ± 1.9 to 5.7 ± 1.8 L/min, p < 0.001) and CI (from 2.7 ± 0.9 to 2.9 ± 1.0 L/min/m², p < 0.001).In patients with CHF, compared to baseline, WWI caused an increase in left atrial volume (from 57 ± 44 to 72 ± 46 mL, p = 0.04), without any changes in left ventricular size or function or amino terminal pro B-type natriuretic peptide. CONCLUSIONS: In patients with CHF, WWI causes an acute increase in cardiac output and a fall in systemic vascular resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02949544) https://clinicaltrials.gov/ct2/show/NCT02949544?cond=NCT02949544&rank=1 .

Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study.

BACKGROUND: Higher cardiorespiratory fitness (CRF) is associated with lower morbidity and mortality in patients with coronary heart disease (CHD). The mechanisms for this are not fully understood. A more favourable cardiometabolic risk factor profile may be responsible; however, few studies have comprehensively evaluated cardiometabolic risk factors in relation to CRF amongst patients with CHD. We aimed to explore differences in cardiometabolic risk and 5-year all-cause mortality risk in patients with CHD who have low, moderate, and high levels of CRF. METHODS: Patients with CHD underwent maximal cardiopulmonary exercise testing, echocardiogram, carotid intima-media thickness measurement, spirometry, and dual X-ray absorptiometry assessment. Full blood count, biochemical lipid profiles, high-sensitivity (hs) C-reactive protein, and NT-proBNP were analysed. Patients were defined as having low, moderate, or high CRF based on established prognostic thresholds. RESULTS: Seventy patients with CHD (age 63.1 ± 10.0 years, 86% male) were recruited. Patients with low CRF had a lower ventilatory anaerobic threshold, peak oxygen pulse, post-exercise heart rate recovery, and poor ventilatory efficiency. The low CRF group also had higher NT pro-BNP, hs-CRP, non-fasting glucose concentrations, and lower haemoglobin and haematocrit. Five-year mortality risk (CALIBER risk score) was also greatest in the lowest CRF group (14.9%). CONCLUSIONS: Practitioners should interpret low CRF as an important clinical risk factor associated with adverse cardiometabolic health and poor prognosis, study registry; www.researchregistry.com .

Non-invasive measurement of right atrial pressure by near-infrared spectroscopy: preliminary experience. A report from the SICA-HF study.

AIMS: To assess the clinical value of measuring right atrial pressure (RAP) using near-infrared spectroscopy (NIRS) in patients with chronic heart failure (CHF). METHODS AND RESULTS: RAP was measured non-invasively using NIRS over the external jugular vein (Venus 1000, Mespere LifeSciences, Canada) in ambulatory patients with CHF enrolled in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) programme. Comparing 243 patients with CHF (mean age 71 years; mean left ventricular ejection fraction (LVEF) 45%, median NT-proBNP 788 ng/L) to 49 controls (NT-proBNP ≤125 ng/L), RAP was 7 [interquartile range (IQR) 4-11] mmHg vs. 4 (IQR 3-8) mmHg (P < 0.001). Those with RAP ≥10 mmHg (n = 75) were older, had more severe clinical congestion and renal dysfunction, higher plasma NT-proBNP, larger left atrial volume, higher systolic pulmonary pressure and were more often in atrial fibrillation but their LVEF was similar to patients with lower RAP. During a median follow-up of 595 (IQR: 492-714) days, 49 patients (20%) died or were hospitalized for worsening CHF. Compared with patients with RAP ≤5 mmHg, those with RAP ≥10 mmHg had a greater risk of an event (hazard ratio 2.38, 95% confidence interval 1.19-4.75, P = 0.014). RAP measured by NIRS predicted outcome, competing with NT-proBNP in multivariable models. CONCLUSIONS: Measuring RAP using NIRS identifies ambulatory patients with CHF who have more severe congestion and a worse outcome. The device might be a useful objective method of monitoring RAP, especially for those inexperienced in eliciting physical signs or when measurement of natriuretic peptides is not immediately available.

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

BACKGROUND: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. METHOD AND RESULTS: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. CONCLUSIONS: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

Prognostic significance of ultrasound-assessed jugular vein distensibility in heart failure.

AIMS: Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically. METHODS AND RESULTS: Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p<0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p<0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93). CONCLUSIONS: Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome. CLINICAL TRIAL REGISTRATION: NCT01872299.

Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.

BACKGROUND: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. METHODS AND RESULTS: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. CONCLUSIONS: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

Global longitudinal strain in patients with suspected heart failure and a normal ejection fraction: does it improve diagnosis and risk stratification?

Many patients have clinical, structural or bio-marker evidence of heart failure (HF) but a normal left ventricular ejection fraction (LVEF; HeFNEF). Measurement of global longitudinal strain (GLS) may add diagnostic and prognostic information. Patients with symptoms suggesting heart failure and LVEF ≥50% were studied: 76 had no substantial cardiac dysfunction (left atrial diameter (LAD) <40 mm and amino-terminal pro-brain natriuretic peptide (NTproBNP) <400 ng/l); 99 had "possible HeFNEF" (LAD ≥40 mm or NTproBNP ≥400 ng/l); and 138 had "definite HeFNEF" (LAD ≥40 mm and NTproBNP ≥400 ng/L). Mean LVEF was 58% in each subgroup. Patients with definite HeFNEF were older, more likely to have atrial fibrillation, had more symptoms and signs of fluid retention, were more likely to have right ventricular dysfunction and had higher pulmonary pressures than other groups. Mean GLS (SD) was less negative in patients with definite HeFNEF (-13.6 (3.0)% vs. possible HeFNEF: -15.2 (3.1)% vs. no substantial cardiac dysfunction: -15.9 (2.4)%; p < 0.001). GLS was -19.1 (2.1)% in 20 controls. During a median follow up of 647 days, cardiovascular death or an unplanned hospitalisation for heart failure occurred in 62 patients. In univariable analysis, GLS but not LVEF predicted events. However, in a multi-variable analysis, only urea, NTproBNP, left atrial volume, inferior vena cava diameter and atrial fibrillation independently predicted adverse outcome. GLS is abnormal in patients who have other evidence of HeFNEF, is associated with a worse prognosis in this population but is not a powerful independent predictor of outcome.

Revisiting a classical clinical sign: jugular venous ultrasound.

BACKGROUND: Increased jugular venous pressure, reflecting the increased right atrial pressure, is a classical sign of heart failure (HF) but clinical assessment may be difficult. METHODS: In ambulatory patients with HF and control subjects, jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, during a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as diameter during Valsalva to that at rest. RESULTS: 211 patients (mean age 70 years; mean left ventricular ejection fraction 43%) and 20 controls were included. JVD (median and inter-quartile [IQR] range) at rest was 0.17 (0.15-0.20) cm in controls and 0.23 (0.17-0.33) cm in patients with HF (p=0.012), JVD ratio was 6.3 (4.3-6.8) in controls and 4.4 (2.7-5.8) in patients with HF (p=0.001).With increasing quartiles of plasma NT-proBNP, JVD at rest rose (0.20 (0.15-0.23) cm, 0.21 (0.16-0.29) cm, 0.25 (0.18-0.35) cm and 0.34 (0.20-0.53) cm (P=<0.001), whilst JVD ratio decreased (5.4 (4.2-6.4), 4.4 (3.5-6.3), 3.9 (2.4-5.4) and 2.8 (1.7-4.7); p=<0.001). JVD ratio correlated with log (NT-proBNP) (r=-0.39, p=<0.001), LV filling pressures (E/E', r=-0.33, p=<0.001) and left atrial volume (r=-0.21, p=0.002). In a multivariable regression model, only trans-tricuspid gradient and TAPSE were independently associated with JVD ratio (R(2)=0.27). CONCLUSIONS: Distension of the JV at rest relative to the maximum diameter during a Valsalva manoeuvre (JVD ratio) identifies patients with heart failure who have higher plasma NT-proBNP levels, right ventricular dysfunction and raised pulmonary artery pressure.

Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure.

BACKGROUND: Prevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown. METHODS AND RESULTS: Of 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0-22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41-75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction. CONCLUSIONS: In patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.

Does the physical examination still have a role in patients with suspected heart failure?

AIMS: The prognostic value of signs of congestion in patients suspected of having chronic heart failure (CHF) is unknown. Our objectives were to define their prevalence and specificity in diagnosing CHF and to determine their prognostic value in patients in a community heart failure clinic. METHODS AND RESULTS: Analysis of referrals to a community clinic for patients with CHF symptoms. Systolic CHF (S-HF) was defined as left ventricular ejection fraction (LVEF) ≤45%, heart failure with normal ejection fraction (HeFNEF) as LVEF > 45%, and amino-terminal pro-brain natriuretic peptide >50 pmol L(-1); other subjects were defined as not having CHF. Signs of congestion were as follows: no signs; right heart congestion (RHC: oedema, jugular venous distension); left heart congestion (LHC: lung crackles); or both (R + LHC). Of 1881 patients referred, 707 did not have CHF, 853 had S-HF, and 321 had HeFNEF. The median inter-quartile range (IQR) age was 72 years (64-78), 40% were women, and LVEF was 47% (35-59). Overall, 417 patients had RHC of whom 49% had S-HF and 21% HeFNEF. Eighty-five patients had LHC of whom 43% had S-HF and 20% had HeFNEF. One hundred and seventy-two patients had R + LHC of whom 71% had S-HF and 16% had HeFNEF. During a median (IQR) follow-up of 64(44-76) months, 40% of the entire patient cohort died. The combination of R + LHC signs was an independent marker of an adverse prognosis (χ(2)-log-rank test = 186.1, P< 0.0001). CONCLUSION: Clinical signs of congestion are independent predictors of prognosis in ambulatory patients with suspected CHF.

Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure.

AIMS: The epidemiology of pulmonary arterial hypertension (PAH) in patients with heart failure (HF) is poorly described. Our aim was to investigate the determinants and prognostic significance of PAH in a large representative outpatient population with HF. METHODS AND RESULTS: Routine measurement of right ventricular tricuspid pressure gradient (RVTG) was attempted among unselected, consecutive referrals to an HF clinic. The diagnosis of HF was based on symptoms, signs, echocardiography, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of 2100 patients referred, 1380 were diagnosed as HF, of whom 1026 had left ventricular systolic dysfunction (LVSD) and 354 did not. Right ventricular tricuspid pressure gradient could be measured in 270 (26%) patients with and 143 (40%) without LVSD. The highest RVTG quartile [RVTG > 35 mmHg equivalent to an estimated PA systolic pressure (PASP) > 45 mmHg] constituted 7% of all those with HF and was associated with higher LV filling pressures, LV end-diastolic volume, LVSD, and more severe mitral regurgitation (MR). During a median (inter-quartile range) follow-up of 66 (56-74) months, mortality was 40.3%. Mortality was similar in the lowest quartile of RVTG and in those in whom RVTG could not be measured and rose with increasing RVTG quartile (log-rank: 26.9; P < 0.0001). The highest RVTG quartile, age, blood pressure, and log NT-proBNP independently predicted mortality. Right ventricular tricuspid pressure gradient >35 mmHg had a 96% specificity to discriminate between those with and without HF in patients without LVSD. CONCLUSION: Using a definition of PASP > 45 mmHg, 7% of the patients with HF have PAH, which is associated with worse LV function, MR, and prognosis. Whether PAH is a target for therapy in this population remains to be elucidated.

Low dose cabergoline for hyperprolactinaemia is not associated with clinically significant valvular heart disease.

OBJECTIVE: Recent trials suggest that using ergot-derived dopamine agonists such as cabergoline in the treatment of Parkinson's disease is associated with an increased risk of valvular heart disease. However, the dose of cabergoline used to treat hyperprolactinaemia is considerably less than that used in Parkinson's disease. DESIGN AND METHODS: A cross-sectional comparative assessment. Forty-four patients treated with cabergoline for hyperprolactinaemia underwent transthoracic echocardiography and were compared with 566 sequential subjects complaining of palpitations, taken from a contemporary echocardiography database. RESULTS: The mean cumulative dose of cabergoline in the cases was 311 mg. There was no significant, severe or moderate, right- or left-sided valvular regurgitation in either group. Left heart: in the mitral and aortic valves, the rate of mild and trivial valvular regurgitation was not different between the two groups. Right heart: mild tricuspid and pulmonary regurgitation on colour Doppler alone was increased significantly in the cabergoline group, odds ratios of 3.1 and 7.8 respectively (95% confidence interval 1.0-9.6 and 0.8-78.4, P=0.04 and P<0.0001 respectively). CONCLUSION: Cabergoline at doses sufficient to suppress hyperprolactinaemia for a period of 3-4 years is not associated with an increased risk of clinically significant valvular regurgitation.