Baseline characteristics of patients with heart failure and preserved ejection fraction included in the Karolinska Rennes (KaRen) study.

Karolinska Rennes (KaRen) is a prospective observational study to characterize heart failure patients with preserved ejection fraction (HFpEF) and to identify prognostic factors for long-term mortality and morbidity. To report characteristics and echocardiography at entry and after 4-8 weeks of follow-up. Patients were included following an acute heart failure presentation with B-type natriuretic peptide (BNP)>100 ng/L or N-terminal pro-BNP (NT-proBNP)>300 ng/L and left ventricular ejection fraction (LVEF)>45%. The mean ± SD age of 539 included patients was 77 ± 9 years and 56% were women. Patient history included hypertension (78%), atrial tachyarrhythmia (44%), prior heart failure (40%) and anemia (37%), but left bundle branch block was rare (3.8%). Median NT-proBNP was 2448 ng/L (n=438), and median BNP 429 ng/L (n=101). Overall, 101 patients did not return for the follow-up visit, including 13 patients who died (2.4%). Apart from older age (80 ± 9 vs. 76 ± 9 years; P=0.006), there were no significant differences in baseline characteristics between patients who did and did not return for follow-up. Mean LVEF was lower at entry than follow-up (56% vs. 62%; P<0.001). At follow-up, mean E/e' was 12.9 ± 6.1, left atrial volume index 49.4±17.8mL/m(2). Mean global left ventricular longitudinal strain was -14.6 ± 3.9%; LV mass index was 126.6 ± 36.2g/m(2). Patients in KaRen were old with slight female dominance and hypertension as the most prevalent etiological factor. LVEF was preserved, but with increased LV mass and depressed LV diastolic and longitudinal systolic functions. Few patients had signs of electrical dyssynchrony (ClinicalTrials.gov.- NCT00774709).

Donal E ，Lund LH ，Oger E ，Hage C ，Persson H ，Reynaud A ，Ennezat PV ，Bauer F ，Sportouch-Dukhan C ，Drouet E ，Daubert JC ，Linde C ，KaRen Investigators ... -  《-》

New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study.

To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study. KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF). We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure. Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012. The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF.

Donal E ，Lund LH ，Oger E ，Hage C ，Persson H ，Reynaud A ，Ennezat PV ，Bauer F ，Drouet E ，Linde C ，Daubert C ，KaRen investigators ... -  《-》

Value of exercise echocardiography in heart failure with preserved ejection fraction: a substudy from the KaRen study.

KaRen is a multicentre study designed to characterize and follow patients with heart failure and preserved ejection fraction (HFpEF). In a subgroup of patients with clinical signs of congestion but left ventricular ejection fraction (LVEF) >45%, we sought to describe and analyse the potential prognostic value of echocardiographic parameters recorded not only at rest but also during a submaximal exercise stress echocardiography. Exercise-induced changes in echo parameters might improve our ability to characterize HFpEF patients. Patients were prospectively recruited in a single tertiary centre following an acute HF episode with NT-pro-BNP >300 pg/mL (BNP > 100 pg/mL) and LVEF > 45% and reassessed by exercise echo-Doppler after 4-8 weeks of dedicated treatment. Image acquisitions were standardized, and analysis made at end of follow-up blinded to patients' clinical status and outcome. In total, 60 patients having standardized echocardiographic acquisitions were included in the analysis. Twenty-six patients (43%) died or were hospitalized for HF (primary outcome). The mean ± SD workload was 45 ± 14 watts (W). Mean ± SD resting LVEF and LV global longitudinal strain was 57.6 ± 9.5% and -14.5 ± 4.2%, respectively. Mean ± SD resting E/e' was 11.3 ± 4.7 and 13.1 ± 5.3 in those patients who did not and those who did experience the primary outcome, respectively (P = 0.03). Tricuspid regurgitation (TR) peak velocity during exercise were 3.3 ± 0.5 and 3.7 ± 0.5 m/s (P = 0.01). Exercise TR was independently associated with HF-hospitalization or death after adjustment on baseline clinical and biological characteristics. Exercise echocardiography may contribute to identify HFpEF patients and especially high-risk ones. Our study suggested a prognostic value of TR recorded during an exercise. That was demonstrated independently of the value of resting E/e'.

Donal E ，Lund LH ，Oger E ，Reynaud A ，Schnell F ，Persson H ，Drouet E ，Linde C ，Daubert C ，KaRen investigators ... -  《-》

Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction.

The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this. The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis. HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes.

Lund LH ，Donal E ，Oger E ，Hage C ，Persson H ，Haugen-Löfman I ，Ennezat PV ，Sportouch-Dukhan C ，Drouet E ，Daubert JC ，Linde C ，KaRen Investigators ... -  《-》

Usefulness of N-terminal pro-brain natriuretic Peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction.

Grewal J ，McKelvie RS ，Persson H ，Tait P ，Carlsson J ，Swedberg K ，Ostergren J ，Lonn E ... -  《AMERICAN JOURNAL OF CARDIOLOGY》