Long-term outcomes in heart failure with preserved ejection fraction: Predictors of cardiac and non-cardiac mortality.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non-CV events, but long-term risk is poorly studied. We assessed incidence and predictors of the long-term CV and non-CV events. METHODS AND RESULTS: Patients presenting with acute HF, EF ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska-Rennes study in 2007-11 and were reassessed after 4-8 weeks in a stable state. Long-term follow-up was conducted in 2018. The Fine-Gray sub-distribution hazard regression was used to detect predictors of CV and non-CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4-8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72-84) years; 52% female], 397 patients were available for the long-term follow-up. Over a median follow-up time from acute presentation of 5.4 (2.1-7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non-CV causes. Incidence rates per 1000 patient-years were 62 [95% confidence interval (CI) 52-74] for CV and 58 (95% CI 48-69) for non-CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non-CV death. From the stable 4-8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non-CV death. CONCLUSIONS: In patients with acute decompensated HFpEF, over 5 years of follow-up, nearly two-thirds of patients died, half from CV and the other half from non-CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non-CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two-thirds' has been inserted before 'of patients died...' in this version.].

Ablation of multifocal premature ventricular contractions using automated pace-mapping software.

INTRODUCTION AND OBJECTIVES: Ablation of multifocal premature ventricular complexes (PVCs) is challenging. Activation mapping can be performed for the predominant morphology, but may be useless for other less prevalent ones. We aimed to describe the efficacy of an automated pace-mapping software-based ablation strategy for ablating the site of origin of multiple PVC locations. METHODS: Consecutive patients referred for ablation of multifocal PVCs were prospectively enrolled. Spontaneous PVC templates were recorded and a detailed pace-mapping map was generated to spot the site of origin of PVCs. RESULTS: A total of 47 PVCs were targeted in 21 patients (five and 16 patients with three or two PVCs morphologies each, respectively). Detailed pace-mapping comprising 73.5±41.6 different pacing locations was performed (best matching 97.2% [IQR 95.9-98.3%] similar to the clinical PVC). Activation points were acquired if possible, although ablation was only based on pace-mapping in 13 (27.6%) foci. Complete acute procedural success was obtained in 14 (66.7%) patients, while one PVC morphology was deliberately not ablated in five patients (23.8%). After 12.3±9.4 months of follow-up, PVC burden decreased from 24.4±10.4% to 5.6±5.0% (p<0.001). Interestingly, patients with acute procedural failures or with some PVCs deliberately not targeted during the procedure also experienced a significant decrease in PVC burden (30.0±8.9% to 11.9±3.5%, p=0.002). CONCLUSION: Quantitative morphology-matching software can be used to obtain a detailed map identifying the site of origin of each single PVC, and successful ablation can be performed at these sites, even if activation points cannot be obtained due to the paucity of ectopic beats.

The effect of cardiac resynchronization without a defibrillator on morbidity and mortality: an individual patient data meta-analysis of COMPANION and CARE-HF.

AIMS: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality for patients with heart failure, reduced left ventricular ejection fraction, QRS duration >130 ms and in sinus rhythm. The aim of this study was to identify patient characteristics that predict the effect, specifically, of CRT pacemakers (CRT-P) on all-cause mortality or the composite of hospitalization for heart failure or all-cause mortality. METHODS AND RESULTS: We conducted an individual patient data meta-analysis of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) and Cardiac Resynchronization-Heart Failure (CARE-HF) trials. Only patients assigned to CRT-P or control (n = 1738) were included in order to avoid confounding from concomitant defibrillator therapy. The influence of baseline characteristics on treatment effects was investigated. Median age was 67 (59-73) years, most patients were men (70%), 68% had a QRS duration of 150-199 ms and 80% had left bundle branch block. Patients assigned to CRT-P had lower rates for all-cause mortality (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.56-0.81; p < 0.0001) and the composite outcome (HR 0.67, 95% CI 0.58-0.78; p < 0.0001). No pre-specified characteristic, including sex, aetiology of ventricular dysfunction, QRS duration (within the studied range) or morphology or PR interval significantly influenced the effect of CRT-P on all-cause mortality or the composite outcome. However, CRT-P had a greater effect on the composite outcome for patients with lower body surface area and those prescribed beta-blockers. CONCLUSIONS: Cardiac resynchronization therapy-pacemaker reduces morbidity and mortality in appropriately selected patients with heart failure. Benefits may be greater in smaller patients and in those receiving beta-blockers. Neither QRS duration nor morphology independently predicted the benefit of CRT-P. CLINICAL TRIAL REGISTRATION: COMPANION, NCT00180258; CARE-HF, NCT00170300.

Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON-HF trial.

AIMS: In the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON-HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios. METHODS AND RESULTS: Eligibility was assessed in the Karolinska-Rennes study (acute HFpEF, LVEF ≥ 45%, and N-terminal pro-B-type natriuretic peptide ≥300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (<54% in women and <52% in men); and (iv) LVEF below mean of normal range (<64% in women and <62% in men). Among 425 patients [age 78 (72-83) years, 57% women, 28% LVEF ≤ 57% (median in PARAGON-HF), the trial scenario, identified 34% as eligible. Left atrial enlargement and/or left ventricular hypertrophy were present in 99%. Inclusion criteria not met were diuretic treatment and New York Heart Association class. Important exclusion criteria were estimated glomerular filtration rate <30 mL/min/1.73 m2 , haemoglobin <10 g/day, and cancer. In the pragmatic scenario, 63% were eligible. In LVEF below lower limit of normal range, 5.4% were eligible, and in LVEF below mean of normal range, 41% were eligible. In patients with LVEF ≤ 57%, eligibility was 42%, 69%, 21%, and 91% according to the trial scenario, pragmatic scenario, LVEF below lower limit of normal range, and LVEF below mean of normal range, respectively. CONCLUSIONS: In real-world HFpEF (LVEF ≥ 45%) with N-terminal pro-B-type natriuretic peptide and cardiac structure/function assessed, eligibility for sacubitril/valsartan was according to PARAGON-HF complete criteria 34%, pragmatic criteria 63%, LVEF below lower limit of normal range 5.4%, and LVEF below mean of normal range 41%. Cardiac structural impairment was almost ubiquitous. Ineligibility was more due to exclusion criteria than failing to meet inclusion criteria.

Predictors of long-term outcome in heart failure with preserved ejection fraction: a follow-up from the KaRen study.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long-term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L in 2007-11. Clinical data were collected at enrolment and after 4-8 weeks including detailed echocardiography. Follow-up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all-cause mortality or HF hospitalization) and secondary (all-cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long-term follow-up data were available for 397 patients [52% female; median (interquartile range) age 79 (73, 84) years]. Over a follow-up of 5.44 (2.06-7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient-years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient-years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) [hazard ratio 1.87 (1.34-2.62)], diabetes mellitus [1.75 (1.11-2.74)], and cancer [1.75 (1.01-3.03)] while female sex was associated with reduced risk [0.64 (0.41-0.98)]. CONCLUSIONS: In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non-cardiac conditions.

Cryoballoon ablation of atrial fibrillation in patients with atypical right pulmonary vein anatomy.

BACKGROUND: Cryoballoon ablation is widely used for pulmonary vein isolation in patients with atrial fibrillation. There are no data regarding the clinical efficacy of cryoballoon ablation in patients with atypical right pulmonary vein anatomy. AIM: We aimed to evaluate the impact of right pulmonary vein anatomy on the safety and efficacy of cryoballoon ablation. METHODS: Patients referred for cryoballoon ablation of paroxysmal atrial fibrillation were enrolled prospectively. Left atrial computed tomography was performed before cryoballoon ablation to determine whether the right pulmonary vein anatomy was "normal" or "atypical". For patients with atypical anatomy, cryoballoon ablation was only performed for right superior and right inferior pulmonary veins, neglecting accessory pulmonary veins. RESULTS: Overall, 303 patients were included: 254 (83.8%) with normal and 49 (16.2%) with atypical right pulmonary vein anatomy. First-freeze isolation for right superior and right inferior pulmonary veins occurred in 44 (89.8%) and 37 (75.5%) patients with atypical pulmonary vein anatomy, and in 218 (85.8%) and 217 (85.4%) patients with typical pulmonary vein anatomy, respectively (P not significant). Phrenic nerve palsies were only observed in patients with normal anatomy (0 vs. 26 [8.6%]; P=0.039). Mid-term survival free from atrial arrhythmia was similar, regardless of right pulmonary vein anatomy. CONCLUSIONS: A significant proportion of patients have atypical right pulmonary vein anatomy. Procedural characteristics, acute pulmonary vein isolation success and mid-term procedural efficacy were similar, regardless of right pulmonary vein anatomy. In addition to left-side pulmonary vein isolation, cryoballoon ablation of right superior and right inferior pulmonary veins only, neglecting accessory pulmonary veins, is sufficient to obtain acute right-side pulmonary vein isolation and mid-term sinus rhythm maintenance in patients with atypical anatomy.

Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients.

AIMS: In heart failure (HF) with preserved ejection fraction (HFpEF), microvascular inflammation is proposed as an underlying mechanism. Myeloperoxidase (MPO) is associated with vascular dysfunction and prognosis in congestive HF. METHODS AND RESULTS: MPO, MPO-related biomarkers, and echocardiography were assessed in 86 patients, 4-8 weeks after presentation with acute HF (EF ≥ 45%), and in 46 healthy controls. Patients were followed up for median 579 days (Q1;Q3 276;1178) regarding the composite endpoint all-cause mortality or HF hospitalization. Patients were 73 years old, 51% were female, EF was 64% (Q1;Q3 58;68), E/e' was ratio 10.8 (8.3;14.0), and left atrial volume index (LAVI) was 43 mL/m2 (38;52). Controls were 60 (57;62) years old (vs. patients; P < 0.001), 24% were female (P = 0.005), and left ventricular EF was 63% (59;66; P = 0.790). MPO was increased in HFpEF compared with controls, 101 (81;132) vs. 86 (74;101 ng/mL, P = 0.015), as was uric acid 369 (314;439) vs. 289 (252;328 µmol/L, P < 0.001), calprotectin, asymmetric dimethyl arginine (ADMA), and symmetric dimethyl arginine (SDMA), while arginine was decreased. MPO correlated with uric acid (r = 0.26; P = 0.016). In patients with E/e' > 14, uric acid and SDMA were elevated (421 vs. 344 µM, P = 0.012; 0.54 vs. 0.47 µM, P = 0.039, respectively), and MPO was 121 vs. 98 ng/mL (P = 0.090). The ratios of arginine/ADMA (112 vs. 162; P < 0.001) and ADMA/SDMA (1.36 vs. 1.17; P = 0.002) were decreased in HFpEF patients, suggesting reduced NO availability and increased enzymatic clearance of ADMA, respectively. Uric acid independently predicted the endpoint [hazard ratio (HR) 3.76 (95% CI 1.19-11.85; P = 0.024)] but not MPO [HR 1.48 (95% CI 0.70-3.14; P = 0.304)] or the other biomarkers. CONCLUSIONS: In HFpEF, MPO-dependent oxidative stress reflected by uric acid and calprotectin is increased, and SDMA is associated with diastolic dysfunction and uric acid with outcome. This suggests microvascular neutrophil involvement mirroring endothelial dysfunction, a central component of the HFpEF syndrome and a potential treatment target.

Heart failure with preserved ejection fraction: A clustering approach to a heterogenous syndrome.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome at the crossroads of multiple co-morbidities; there is no valid treatment for this condition. Defining new phenotypes could play a role in improving treatment and prognosis. AIM: To identify groups with different pathophysiologies by applying a clustering approach to a multicentric cohort of patients with HFpEF. METHODS: A total of 538 patients from the multicentre KaRen study were included. Accurate clinical, biological and ultrasound data are available, with a mean follow-up of 28 months. Based on a clustering analysis, the population was separated into groups based on 55 variables, comparing distribution of deaths and hospitalizations between groups. RESULTS: Three clusters were identified from 356 analysable patients (mean age 76.1±9.31 years; 43.5% men): cluster 1 (n=128) comprised overweight, relatively young men at high cardiovascular risk, in sinus rhythm, with altered renal function; cluster 2 (n=134) comprised women, most of whom had conserved left ventricular function; cluster 3 (n=94) had the highest incidence of mitral regurgitation, atrial remodelling and rhythm disorders. There were no significant differences, only a trend towards early mortality in cluster 3. CONCLUSIONS: Clustering analysis seems to be effective at individualizing subgroups with different physiopathologies in HFpEF. The clinical relevance of these phenotypes needs to be studied, and may concern treatment strategy more than prognostic differences.

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning.

OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups. METHODS: We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71-83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses. RESULTS: We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95% CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8-2.9); 5.7 (2.6-12.8); 2.9 (1.5-5.6); 2.7 (1.6-4.6); 2.1 (1.2-3.9)). CONCLUSIONS: Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.

Do Patients With Acute Heart Failure and Preserved Ejection Fraction Have Heart Failure at Follow-Up: Implications of the Framingham Criteria.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) may be misdiagnosed. We assessed prevalence and consistency of Framingham criteria signs and symptoms in acute vs subsequent stable HFpEF. METHODS: Three hundred ninety-nine patients with acute HFpEF according to Framingham criteria were re-assessed in stable condition. Four definitions of HFpEF at follow-up: (1) Framingham criteria alone, (2) Framingham criteria and natriuretic peptides (NPs), (3) Framingham criteria, NPs, and European Society of Cardiology HF guidelines echocardiographic criteria, (4) Framingham criteria, NPs, and the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON) trial echocardiographic criteria. RESULTS: At follow-up, HFpEF was still present in 27%, 22%, 21%, and 22%, respectively. Most prevalent in acute HFpEF were dyspnea at exertion (90%), pulmonary rales (71%), persisting at follow-up in 70% and 13%, respectively. Characteristics at acute HF with greater or lesser odds of stable HFpEF; (1) jugular venous distention (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.13-2.87; P = .013) and pleural effusion (OR 0.45, 95% CI 0.24-0.85; P = .014) and (4), older age (1.04, 95% CI 1.01-1.08; P = .014) and tachycardia (>100 bpm) 0.52, 95% CI 0.27-1.00; P = .048). CONCLUSIONS: In patients with acute HFpEF, one-quarter met the HF definition according to Framingham criteria at ambulatory follow-up. The proportion of patients with postdischarge HFpEF was largely unaffected by additional echocardiographic or NP criteria Older age and jugular venous distention at acute presentation predicted persistent HFpEF at follow-up, whereas pleural effusion and tachycardia may yield false HFpEF diagnoses. This finding has implications for HFpEF trial design.

The challenging right inferior pulmonary vein: A systematic approach for successful cryoballoon ablation.

BACKGROUND: Pulmonary vein isolation (PVI) using cryoballoon ablation is widely used for rhythm control in patients with paroxysmal atrial fibrillation. This technique has a steep learning curve, and PVI can be achieved quickly in most patients. However, the right inferior pulmonary vein (RIPV) is often challenging to occlude and isolate. AIM: We aimed to analyse the efficacy of RIPV ablation using a systematic approach. METHODS: Consecutive patients referred for cryoballoon ablation of paroxysmal atrial fibrillation were enrolled prospectively. A systematic approach was used for RIPV cryoablation. The primary endpoint was acute RIPV isolation during initial freeze. RESULTS: A total of 214 patients were included. RIPV isolation during initial freeze occurred in 179 patients (82.2%). Real-time PVI could be observed in 72 patients (33.6%), whereas cryoballoon stability required pushing the Achieve™ catheter inside the RIPVs in the remaining patients. The rate of unsuccessful or aborted first freeze as a result of insufficient minimal temperature was significantly higher in patients with real-time pulmonary vein potential recording (16.7% vs. 6.3%; P=0.031). To overcome this issue and obtain both stability and real-time PVI, a dedicated "whip technique" was developed. Twelve patients (5.6%) required a redo ablation; only two of these had a reconnected RIPV. CONCLUSIONS: A systematic approach to RIPV cryoablation can lead to a high rate of first freeze application. Operators should not struggle to visualize pulmonary vein potentials before ablation, as this may decrease cryoapplication efficacy. Thus, stability should be preferred over real-time PVI for RIPV ablation. Both stability and real-time PVI can be obtained using a "whip technique".

Localization of Residual Conduction Gaps After Wide Antral Circumferential Ablation of Pulmonary Veins.

Ablation of atrial fibrillation (AF) is the cornerstone therapy for patients with symptomatic AF resistant to anti-arrhythmic drugs or as first-line therapy, and is based on permanent pulmonary vein (PV) isolation. The presence of a conduction gap in a wide antral circumferential ablation lesion around PVs is often sufficient to transform an initially successful ablation into a procedural failure, thus necessitating a redo intervention. The strategy during a redo procedure is based on the detection and ablation of the reconnection gap. Finding gaps is often simple, but also sometimes challenging, because gaps may be difficult to detect, resulting in unnecessary radiofrequency delivery. The present review aimed to describe the various techniques published thus far to detect residual reconnections along the encircling ablation lines around PVs, to help electrophysiologists to detect and ablate reconnection gaps.

Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction.

AIMS: This study aims to assess prognostic impact of Framingham criteria for heart failure (FC-HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF). METHODS AND RESULTS: In the prospective Karolinska-Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all-cause mortality and HF hospitalization. The descriptive models were FC-HF alone, FC-HF + natriuretic peptides (NPs) according to the PARAGON trial, FC-HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC-HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4-8 weeks, 13 (2.4%) patients died before the planned follow-up, and 88 patients (16%) declined or were unable to return. Three hundred ninety-nine patients have FC registered at follow-up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC-HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1-4 had to fulfil the FC-HF. The patients in model 0 did not fulfil the criteria for FC-HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47-7.76, P = 0.004]. Patients without FC-HF had better prognosis than patients meeting FC-HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14-2.09, P = 0.005; HR 1.71, 95% CI 1.24-2.36, P = 0.002; HR 1.95, 95% CI 1.36-2.81, P = 0.001; and HR 2.05, 95% CI 1.45-2.91, P < 0.001, for descriptive models 1-4, respectively. No descriptive model independently predicted the endpoint. CONCLUSIONS: In ambulatory HFpEF patients, a quarter met FC-HF, while most met NP and echocardiography criteria for HF. Residual FC-HF tended to be associated with increased risk for mortality and HF hospitalization, further strengthened by NPs and echocardiographic criteria, highlighting its role in clinical risk assessment.

ST2 in heart failure with preserved and reduced ejection fraction.

OBJECTIVES: Soluble suppression of tumorigenecity 2 (sST2) is prognostic in acute and chronic heart failure with reduced ejection fraction (HFrEF) but less studied in HF with preserved EF (HFpEF). We evaluated sST2 concentrations, correlations with biomarkers and echocardiographic measures of diastolic and systolic function, and associations with outcomes in HFpEF and HFrEF. DESIGN AND RESULTS: A total of 193 subjects from three different cohorts were included. Eighty-six HFpEF patients were obtained from the Karolinska Rennes (KaRen) study, 86 patients with HFrEF were recruited from referrals to Karolinska University Hospital for advanced assessment of HF, and 21 controls were included (ClinicalTrials.gov Identifier for KaRen: NCT01091467). HFrEF and controls cohorts did not have ClinicalTrials.gov registrations. sST2 was lower in HFpEF, median (interquartile range); 23 (17-31) compared to HFrEF; 35 (23-52) µg/L, p < .001. In both HFpEF and HFrEF, sST2 correlated positively with NT-proBNP (HFpEF rs=0.392, p < .001 and HFrEF rs=0.466, p < .001). In HFpEF, sST2 correlated to left atrial volume index (rs=0.276, p = .019) but not to E/E´, nor to left ventricular mass index. sST2 was in HFpEF associated with the composite endpoint of death or HF hospitalization, adjusted hazard ratio (HR) per log increase in sST2 6.62, 95% confidence interval (CI) 1.04-42.28, p = .046, and in HFrEF death, heart transplant or left ventricular assist systems; 3.51, 95% CI 1.05-11.69, p = .041. CONCLUSIONS: In patients with HFpEF compared to HFrEF, crude levels of sST2 were lower but potentially more strongly associated with outcomes. The lower levels of sST2 in HFpEF than in HFrEF may reflect lower degrees of fibrosis, but the potentially stronger association with outcomes may reflect a greater prognostic importance of progressive fibrosis and as such a greater potential for intervention. In conclusion; this study adds to the evidence of sST2 as prognostic marker in both HFpEF and HFrEF.

Radiofrequency ablation of right ventricular tachycardia in patients with no femoral access: safety and efficacy of a superior approach.

AIMS: Ventricular tachycardia (VT) ablation has been proven to be effective and safe to avoid arrhythmia recurrences in patients with repaired congenital heart disease (CHD). However, some of these patients may present right ventricular (RV) access issues [agenesia or thrombosis of inferior vena cava (IVC)], making impossible to access the right ventricle through an inferior approach. In such patients, only a superior approach would theoretically be feasible. METHODS AND RESULTS: All VT ablations performed through a jugular or subclavian approach in CHD patients between 2012 and 2017 were included. Among 247 patients scheduled for VT ablation, two patients underwent three VT ablation procedures via a superior approach for due to the inability to access the right ventricle through a conventional IVC access (IVC interruption with azygos continuation in one patient and IVC thrombosis in the other). Ablation was performed using a three-dimensional system through a superior approach, using a subclavian access in both cases. A redo ablation had to be performed in the first patient using a jugular approach. Large curve catheters were used to facilitate RV outflow tract access. Supposed critical isthmuses could be localized and ablated. Patients remained free from arrhythmias during follow-up. CONCLUSION: In patients with repaired CHD and 'no femoral access', ablation of RV tachycardia can be performed using a subclavian or a jugular approach. Mapping may be challenging, requiring large curve catheters. Conventional isthmuses can be mapped and ablated successfully, and such patients should not be denied radiofrequency ablation.

Importance of structural heart disease and diastolic dysfunction in heart failure with preserved ejection fraction assessed according to the ESC guidelines - A substudy in the Ka (Karolinska) Ren (Rennes) study.

AIMS: To study prevalence and prognostic importance of diagnostic echocardiographic variables in patients with suspected heart failure with preserved ejection fraction (HFpEF) in the prospective KaRen register study. METHODS AND RESULTS: KaRen patients were included following an acute HF-presentation, using Framingham criteria, B-type natriuretic peptide (BNP) >100 ng/L or N-terminal pro-BNP (NT-pro-BNP) >300 ng/L, and left ventricular (LV) ejection fraction ≥45%. Echocardiography was performed after 4-8 weeks and analyzed at a core laboratory. In this substudy HFpEF was diagnosed according to the ESC guidelines for heart failure 2016. A total of 539 patients were included with a follow-up after 4-8 weeks in 438 patients. Complete echocardiography and ECG were available in 356 patients. At least two abnormal echocardiographic criteria for HFpEF were found in 94% (n = 333). Echocardiographic signs of structural heart disease and diastolic dysfunction according to 4 criteria by ESC were found in 76% (n = 270). Diastolic dysfunction was graded as mild in 30% (n = 107), moderate in 27% (n = 97) or severe in 35% (n = 124). After multivariate analyses with adjustment for age, gender, EF and natriuretic peptides we found two independent predictors of worse prognosis: presence of moderate and severe diastolic dysfunction (HR 1.8, CI 1.2-2.7, p = 0.0037) and presence of a high number (≥4) of abnormal diastolic parameters (HR 2.0, CI 1.3-3.1, p = 0.0033). CONCLUSION: The majority of KaRen patients with suspected HFpEF had diagnostic echocardiographic criteria for HFpEF according to ESC Guidelines. Our findings support using 2016 ESC HF guidelines for risk prediction in HFpEF.

Procedural safety and long-term follow-up after pacemaker implantation in nonagenarians.

BACKGROUND: The rate of pacemaker (PM) implantations is constantly growing. Since life expectancy of the population is projected to increase, a large number of nonagenarian patients will need PM implantation. We aimed at analyzing short- and long-term outcomes after PM implantation in nonagenarians. METHODS: Patients aged ≥90 years referred for PM implantation from 2004 to 2017 were included. The primary clinical endpoint was total mortality. Secondary endpoints included procedure-related and in-hospital complications. RESULTS: A total of 172 patients were included (92.6 ± 2.1 years, from 90.0 to 101.4 years). Procedure duration was 50.0 ± 19.7 minutes. Most of the patients had VVI devices implanted (143 pts, 83.1%) and mean hospital stay was 3.5 ± 1.5 days. Nine patients (5.2%) had short-term device-related complications and 29 patients (16.8%) had post-procedural complications, non-related to the implantation, including four leading to patients' death. During a follow-up of 22.5 months (interquartile range: 7.3-38.0), 94 patients (54.7%) died. Survival rates were 82.9% (95% confidence interval [CI]: 76.0-88.0), 73.7% (95% CI: 65.7-80.1) and 37.5% (95% CI: 27.5-47.5) after 1, 2, and 5 years, respectively. The Charlson comorbidity index was a predictive factor of procedural complications (odds ratio = 1.33; 95% CI: 1.05-1.69, P = 0.02) while having a complication (hazard ratio [HR] = 4.04; 95% CI: 1.79-9.11, P = 0.001) and atrial fibrillation (HR = 1.63; 95% CI: [1.02-2.63], P = 0.043) were predictors of post-implantation death. CONCLUSION: PM implantation in nonagenarians is safe, with a low risk of procedural complications, but many comorbidities-related complications can occur. Caution should be taken in this old and frail population since complications significantly impact patients' survival.

Patient reported outcome in HFpEF: Sex-specific differences in quality of life and association with outcome.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with poor quality of life (QoL), or patient reported outcome (PRO). Despite female predominance in HFpEF, sex-specific differences in PROs remain poorly studied. We assessed PRO measures and their association with HF-severity and outcome in HFpEF by sex. METHODS AND RESULTS: In 378 patients with HFpEF from the KaRen study, EQ-5D-3L® and Minnesota Living with Heart Failure Questionnaire® (MLHFQ) were assessed. Characteristics and comorbidities were largely similar in women (n = 212, 57%) and men. Women expressed worse QoL in EQ-5D-3L®(EQ-VAS), independent of age and HF-severity, mean (SD), 57 (20) vs. 61 (19), p = 0.010. There was no difference in MLHFQ, 31 (21) vs. 29 (21), p = 0.269. Spearman's correlations with HF-severity (NYHA-class) were for MLHFQ in women rs 0.37 vs. men 0.41, p for both <0.001, and for EQ-VAS rs -0.28, p = 0.001 vs. -0.45, p < 0.001. Correlations with natriuretic peptides were for MLHFQ rs 0.21, p = 0.003 in women vs. men 0.27, p < 0.001, and for EQ-VAS rs -0.17 vs. -0.27, p both < 0.001. Associations between PRO and the composite of HF hospitalisation or all-cause death were present in men only, adjusted HR per 5 units increase in MLHFQ 1.06, 95% confidence interval (CI) 1.01-1.11, p = 0.02 and EQ-VAS, HR 0.93, 95% CI 0.88-0.98, p = 0.010. CONCLUSION: In HFpEF, women had worse general but similar disease specific QoL compared to men. QoL was more strongly associated with HF-severity in men, and associated with outcomes only in men. In women with HFpEF, QoL appears less determined by HF itself and potentially more by other unknown factors.