Multi-modality assessment of congestion in acute heart failure: Associations with left ventricular ejection fraction and prognosis.

BACKGROUND: Integrating clinical examination with ultrasound measures of congestion could improve risk stratification in patients hospitalized with acute heart failure (AHF). AIM: To investigate the prevalence of clinical, echocardiographic and lung ultrasound (LUS) signs of congestion according to left ventricular ejection fraction (LVEF) and their association with prognosis in patients with AHF. METHODS: We pooled the data of four cohorts of patients (N = 601, 74.9±10.8 years, 59 % men) with AHF and analysed six features of congestion at enrolment: clinical (peripheral oedema and respiratory rales), biochemical (BNP/NT-proBNP≥median), echocardiographic (inferior vena cava (IVC)≥21 mm, pulmonary artery systolic pressure (PASP)≥40 mmHg, E/e'≥15) and B-lines ≥25 (8-zones) in those with reduced (<40 %, HFrEF), mildly reduced (40-49 %, HFmrEF and preserved (≥50 %HFpEF) LVEF. RESULTS: Compared to patients with HFmrEF (n = 110) and HFpEF (n = 201), those with HFrEF (N = 290) had higher natriuretic peptides, but prevalence of clinical (39 %), echocardiographic (IVC≥21 mm: 56 %, E/e'≥15: 57 %, PASP≥40 mmHg: 76 %) and LUS (48 %) signs of congestion was similar. In multivariable analysis, clinical (HR: 3.24(2.15-4.86), p < 0.001), echocardiographic [(IVC≥21 mm (HR:1.91, 1.21-3.03, p=0.006); E/e'≥15 (HR:1.54, 1.04-2.28, p = 0.031)] and LUS (HR:2.08, 1.34-3.24, p = 0.001) signs of congestion were significantly associated with all-cause mortality and/or HF re-hospitalization. Adding echocardiographic and LUS features of congestion to a model than included age, sex, systolic blood pressure, clinical congestion and natriuretic peptides, improved prediction at 90 and 180 days. CONCLUSIONS: Clinical and ultrasound signs of congestion are highly prevalent in patients with AHF, regardless of LVEF and their combined assessment improves risk stratification.

Assessment of filling pressures and fluid overload in heart failure: an updated perspective.

Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.

Assessment of Patient Knowledge, Awareness, and Adherence in Heart Failure in a Real-Life Setting: Insights from Data Acquired in Pharmacies.

BACKGROUND: Patient knowledge is crucial for managing and/or monitoring patients with heart failure (HF). However, "real-life" evidence of knowledge level and awareness in HF is yet to be explored. We assessed unselected HF patients' knowledge and awareness in a pharmacy setting. METHODS: One hundred eight HF patients (mean age [SD], 70 (12) years, 61% men) were studied in pharmacies in the north-east region of France in 2019. All patients were interviewed by their pharmacist to quantify their knowledge in HF, self-assessment of symptoms of congestion, as well as their adherence to HF treatment and guideline-recommended lifestyle. RESULTS: Overall, 40% of patients had not consulted their cardiologist in the past 6 months, and 89% never underwent an HF education program. Regarding HF knowledge, nearly half were unsure whether they had HF (43.5%). Only half of the patients knew how to self-assess HF symptoms (57.4%), while a quarter (25%) were unsure of the purpose of HF medications. CONCLUSIONS: In patients with HF assessed in their pharmacies, a majority lacked fundamental knowledge regarding HF, such as self-assessment of congestion, possibly due to a minimal proportion of patients undergoing an HF education program. These results suggest that interventions led by pharmacies may help improve HF education coverage in patients who may have poor access to specialized care.

Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial.

AIMS: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial. METHODS AND RESULTS: Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesspiro/control : -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m2 ; interaction pacross-tertiles  = 0.005; interaction pthird tertile  = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differencesspiro/control : -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction pacross-tertiles  = 0.09; interaction pthird tertile < 0.001]. CONCLUSIONS: These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).

Integrative Assessment of Congestion in Heart Failure Throughout the Patient Journey.

Congestion is one of the main predictors of poor patient outcome in patients with heart failure. However, congestion is difficult to assess, especially when symptoms are mild. Although numerous clinical scores, imaging tools, and biological tests are available to assist physicians in ascertaining and quantifying congestion, not all are appropriate for use in all stages of patient management. In recent years, multidisciplinary management in the community has become increasingly important to prevent heart failure hospitalizations. Electronic alert systems and communication platforms are emerging that could be used to facilitate patient home monitoring that identifies congestion from heart failure decompensation at an earlier stage. This paper describes the role of congestion detection methods at key stages of patient care: pre-admission, admission to the emergency department, in-hospital management, and lastly, discharge and continued monitoring in the community. The multidisciplinary working group, which consisted of cardiologists, emergency physicians, and a nephrologist with both clinical and research backgrounds, reviewed the current literature regarding the various scores, tools, and tests to detect and quantify congestion. This paper describes the role of each tool at key stages of patient care and discusses the advantages of telemedicine as a means of providing true integrated patient care.

Hyperkalaemia prevalence, recurrence and management in chronic haemodialysis: a prospective multicentre French regional registry 2-year survey.

BACKGROUND: Observational studies have reported increased mortality rates in hyperkalaemic or hypokalaemic chronic haemodialysis patients. This study assessed the prevalence and recurrence of hyperkalaemia (HK) along with the concomitant prescription of low-potassium (K) dialysis baths and of K-binding agents in a registry within a French regional disease management programme. METHODS: This was a prospective multicentre (14 chronic haemodialysis centres, Lorraine Region) study encompassing 527 chronic haemodialysis patients followed from 2 January 2014 to 31 December 2015. Predialysis serum K (14 734) measurements, dialysis bath K concentrations and concomitant K binder prescriptions were collected with an electronic health record system. RESULTS: At baseline, 26.4%, 13.8% and 4.9% of patients were hyperkalaemic (i.e. K >5.1, 5.5 or 6 mmol/L, respectively) and 12.5%, 1.9% and 0.4% were hypokalaemic (i.e. K<4, 3.5 or 3 mmol/L, respectively). A total of 61% of patients were prescribed a K-binding resin [essentially sodium polystyrene sulfonate (SPS)], while 2 mmol/L and 3 mmol/L K concentration baths were used relatively equally. Over time, the proportion of patients being prescribed any K-binding agent increased up to 78%. The percentage of patients experiencing HK at any time was 73.8% (HK >5.1 mmol/L), 57.9% (HK >5.5 mmol/L) and 34.5% (HK >6 mmol/L). Only 6.3% of patients became normokalaemic within 3 months after an HK >5.5 mmol/L despite dynamic management of K baths and K binders (i.e. increased prescription of 2 mmol/L K baths and increased SPS doses). CONCLUSIONS: HK was found to be highly prevalent and recurrent in this regional registry despite the widespread and dynamic prescription of low-K dialysis baths and K binders. More effective potassium mitigating strategies are eagerly warranted.

Reproducibility of echocardiographic assessment of 2D-derived longitudinal strain parameters in a population-based study (the STANISLAS Cohort study).

Global peak systolic longitudinal strain (PLS) derived from speckle tracking echocardiography (STE) is a widely used left ventricular deformation parameter. Modern ultrasound systems with improved temporal resolution and new software now allow automated multilayer analysis; however, there is limited evidence regarding its reproducibility. We performed intra- and inter-observer analyses within a population-based cohort study using conventional quantitative strain analysis (GE Healthcare). Fifty patients (49 ± 14 years) were randomly selected among the fourth visit of the STANISLAS Cohort. Multilayer PLS (transmural, subendocardial, and subepicardial), and strain rate (peak systolic, early and late diastolic) were evaluated. Peak systolic shortening (PSS) and early positive systolic strain (EPS) were calculated, as well as post-systolic index (PSI) and pre-stretch index (PST), two additional strain-derived parameters. Intra-observer intraclass correlation coefficients (ICC) were >0.75 for all analyzed parameters. The mean relative intra-observer differences were <5% for all considered parameters, and their 1.96 SDs were <15% for multilayer PLS, strain rate and PSS, but not for EPS, PSI and PST. Inter-observer ICCs were >0.70 (the majority being >0.80). The mean relative inter-observer differences were <7.5% for all considered parameters, with 1.96 SDs of relative differences being <21% for multilayer PLS, strain rate and PSS, but not for EPS, PSI and PST. In this population-based study, in subjects without or with a limited number of cardiovascular risk factors and no previous cardiovascular events, deformation parameters were found to be highly reproducible, except for EPS, PSI and PST, which showed moderately higher variability. Quantitative strain analysis appears to be an effective clinical and research tool, providing insights regarding longitudinal deformation using a simple three-step post-processing procedure.

Cumulative Effects of Several Target Organ Damages in Risk Assessment in Hypertension.

BACKGROUND: The prognostic value of screening multiple target organ damages (TODs) in hypertensive subjects has not been extensively studied. We estimated the prognostic value of considering 3 TODs in estimating the 10-year survival in hypertensive subjects. METHODS: At baseline 1,848 out of a cohort of 1,963 hypertensive patients had a previous cardiovascular disease (CVD) or assessments of 3 TODs: Modification in Diet in Renal Disease (MDRD) <60ml/min or albuminuria >300mg/day, Sokolow index >3.5 mV, and advanced hypertensive retinopathy (grades 3 and 4 of Keith-Wagener-Barker classification). The cohort was divided into 5 groups: 0 TOD (N = 978), 1 TOD (N = 308), 2 TODs (N = 94), 3 TODs (N = 30), and previous CVD (N = 438). RESULTS: After 10 years of follow-up, we observed 418 deaths of which 254 from cardiovascular cause. The adjusted hazard ratios for the major cardiovascular risk factors showed a progressive risk associated with the number of TODs. For all-cause death, the hazard ratios [95% confidence intervals] vs. 0 TOD of the other 4 groups were 1.91 [1.39-2.63], 1.99 [1.28-3.10], 4.33 [2.42-7.72], and 3.09 [2.35-4.05], respectively. For cardiovascular death, the hazard ratios [95% confidence intervals] were of the same order of magnitude: 2.14 [1.38-3.32], 2.12 [1.15-3.89], 4.22 [1.83-9.72], and 4.24 [2.95-6.11], respectively. CONCLUSIONS: Our results indicate that hypertensive patients with several TODs had a worst outcome. Thus, it seems important to screen for multiple TODs in hypertension; especially check for severe hypertensive retinopathy in patients with left ventricular hypertrophy (LVH) and renal damage.

Assessment of Left Ventricular Ejection Fraction Calculation on Long-axis Views From Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction.

To assess left ventricular ejection fraction (LVEF) accurately, cardiac magnetic resonance (CMR) can be indicated and lays on the evaluation of multiple slices of the left ventricle in short axis (CMRSAX). The objective of this study was to assess another method consisting of the evaluation of 2 long-axis slices (CMRLAX) for LVEF determination in acute myocardial infarction.One hundred patients underwent CMR 2 to 4 days after acute myocardial infarction. LVEF was computed by the area-length method on horizontal and vertical CMRLAX images. Those results were compared to reference values obtained on contiguous CMRSAX images in one hand, and to values obtained from transthoracic echocardiography (TTE) in the other hand. For CMRSAX and TTE, LVEF was computed with Simpson method. Reproducibility of LVEF measurements was additionally determined. The accuracy of volume measurements was assessed against reference aortic stroke volumes obtained by phase-contrast MR imaging.LVEF from CMRLAX had a mean value of 47 ±â€Š8% and were on average 5% higher than reference LVEF from CMRSAX (42 ±â€Š8%), closer to routine values from TTELAX (49 ±â€Š8%), much better correlated with the reference LVEF from CMRSAX (R = 0.88) than that from TTE (R = 0.58), obtained with a higher reproducibility than with the 2 other techniques (% of interobserver variability: CMRLAX 5%, CMRSAX 11%, and TTE 13%), and obtained with 4-fold lower recording and calculation times than for CMRSAX. Apart from this, CMRLAX stroke volume was well correlated with phase-contrast values (R = 0.81).In patients with predominantly regional contractility abnormalities, the determination of LVEF by CMRLAX is twice more reproducible than the reference CMRSAX method, even though the LVEF is consistently overestimated compared with CMRSAX. However, the CMRLAX LVEF determination provides values closer to TTE measurements, the most available and commonly used method in clinical practice, clinical trials, and guidelines in ischemic cardiomyopathy. Moreover, LVEF determination by CMRLAX allows a 63% gain of acquisition/reading time compared with CMRSAX. Thus, despite the fact that LVEF obtained from CMRSAX remains the gold standard, CMRLAX should be considered to shorten the overall imaging acquisition and reading time as a putative replacement.

Geographic differences in heart failure trials.

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity.

Usefulness of Speckle-Tracking Imaging for Right Ventricular Assessment after Acute Myocardial Infarction: A Magnetic Resonance Imaging/Echocardiographic Comparison within the Relation between Aldosterone and Cardiac Remodeling after Myocardial Infarction Study.

BACKGROUND: Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is frequent and associated with poor prognosis. The complex anatomy of the right ventricle makes its echocardiographic assessment challenging. Quantification of RV deformation by speckle-tracking echocardiography is a widely available and reproducible technique that readily provides an integrated analysis of all segments of the right ventricle. The aim of this study was to investigate the accuracy of conventional echocardiographic parameters and speckle-tracking echocardiographic strain parameters in assessing RV function after AMI, in comparison with cardiac magnetic resonance imaging (CMR). METHODS: A total of 135 patients admitted for AMI (73 anterior, 62 inferior) were prospectively studied. Right ventricular function was assessed by echocardiography and CMR within 2 to 4 days of hospital admission. Right ventricular dysfunction was defined as CMR RV ejection fraction < 50%. Right ventricular global peak longitudinal systolic strain (GLPSS) was calculated by averaging the strain values of the septal, lateral, and inferior walls. RESULTS: Right ventricular dysfunction was documented in 20 patients. Right ventricular GLPSS was the best echographic correlate of CMR RV ejection fraction (r = -0.459, P < .0001) and possessed good diagnostic value for RV dysfunction (area under the receiver operating characteristic curve [AUROC], 0.724; 95% CI, 0.590-0.857), which was comparable with that of RV fractional area change (AUROC, 0.756; 95% CI, 0.647-0.866). In patients with inferior myocardial infarctions, the AUROCs for RV GLPSS (0.822) and inferolateral strain (0.877) were greater than that observed for RV fractional area change (0.760) Other conventional echocardiographic parameters performed poorly (all AUROCs < 0.700). CONCLUSIONS: After AMI, RV GLPSS is the best correlate of CMR RV ejection fraction. In patients with inferior AMIs, RV GLPSS displays even higher diagnostic value than conventional echocardiographic parameters.

Reproducibility in echocardiographic assessment of diastolic function in a population based study (the STANISLAS Cohort study).

INTRODUCTION: There is limited evidence regarding intra-observer and inter-observer variations in echocardiographic measurements of diastolic function. This study aimed to assess this reproducibly within a population-based cohort study. METHODS: Sixty subjects in sinus rhythm were randomly selected among 4th visit participants of the STANISLAS Cohort (Lorraine region, France). This 4th examination systematically included M-mode, 2-dimensional, DTI and pulsed-wave Doppler echocardiograms. Reproducibility of variables was studied by intra-class correlation coefficients (ICC) and Bland Altman plots. RESULTS: Our population was on average middle-aged (50 ± 14 y), overweight (BMI = 26 ± 6 kg/m2) and non-smoking (87%) with a quarter of the participants having self-declared hypertension or treated with anti-hypertensive medication(s). Intra-observer ICC were > 0.90 for all analyzed parameters except for left ventricular ejection fraction (LVEF) which was 0.89 (0.81-0.93). The mean relative intra-observer differences were small and limits of agreement of relative differences were narrow for all considered parameters (<5% and <15% respectively). Inter-observer ICC were > 0.90 for all analyzed parameters except for LVEF (ICC = 0.87) and both mitral and pulmonary A wave duration (0.83 and 0.73 respectively). The mean relative inter-observer differences were <5% for all parameters except for pulmonary A wave duration (mean difference = 6.5%). Limits of agreement of relative differences were narrow (<15%), except for mitral A wave duration and velocity (both <20%) as well as left ventricular mass and pulmonary A wave duration (both <30%). Intra-observer agreements with regard to the presence and severity of diastolic dysfunction were excellent (Kappa = 0.93 (0.83-1.00) and 0.88 (0.75-0.99), respectively). CONCLUSION: In this validation study within the STANISLAS cohort, diastolic function echocardiographic parameters were found to be highly reproducible. Diastolic dysfunction consequently appears as a highly effective clinical and research tool.

Assessment of right ventricular functional recovery after acute myocardial infarction by 2D speckle-tracking echocardiography.

To assess the pattern of right ventricular (RV) functional recovery in a cohort of patients with successful reperfusion of a first episode of acute myocardial infarction (AMI) with 2D speckle-tracking echocardiography and cardiac magnetic resonance imaging (CMR). Ninety-five revascularized AMI patients were prospectively included (56.8 ± 11.1 years, 48 inferior, 47 anterior). RV function was assessed by echocardiography and CMR within the initial 72 h and 6 months later. A RV global strain was calculated while averaging strain values from septal, lateral and inferior walls. At the acute phase, RVEFCMR was lower in inferior than in anterior AMI patients (52.5 ± 6.8 vs. 56.0 ± 4.8, p = 0.006). Similarly, RV global, inferior and lateral strains were lower in inferior MI patients (p < 0.001 for all) whereas septal strain was not significantly different across groups. At 6 months, RVEFCMR and all strain parameters improved compared to baseline. Improvements were more substantial for patients with inferior than with anterior MI. RV parameters ultimately reached similar levels in the two groups at 6 months except for inferior strain which remained lower in patients with inferior MI (-24.5 ± 6.5 vs. -27.5 ± 5.4, p = 0.03). In low risk patients after AMI, RV function ultimately recovered over the 6 months of follow up. Higher levels of both initial impairment and subsequent recovery were observed for inferior MI. Although RV function was relatively preserved in these patients, RV strain analysis revealed a persistent impairment of RV inferior strain in patients with inferior MI, which may not be identified by RVEFCMR or conventional echocardiographic parameters.

Prophylactic radiofrequency ablation in asymptomatic patients with Wolff-Parkinson-White is not yet a good strategy: a decision analysis.

BACKGROUND: Therapeutic management of asymptomatic patients with a Wolff-Parkinson-White (WPW) pattern is controversial. We compared the risk:benefit ratios between prophylactic radiofrequency ablation and no treatment in asymptomatic patients with WPW. METHODS AND RESULTS: Decision analysis software was used to construct a risk-benefit decision tree. The target population consisted of 20- to 40-year-old asymptomatic patients with WPW without structural fatal heart disease or a family history of sudden cardiac death. Baseline estimates of sudden death and radiofrequency ablation complication rates were obtained from the literature, an empirical data survey, and expert opinion. The outcome measure was death within 10 years. Sensitivity analyses determined the variables that significantly impacted the decision to ablate or not. Threshold analyses evaluated the effects of key variables and the optimum policy. At baseline, the decision to ablate resulted in a reduction of mortality risk of 8.8 patients for 1000 patients compared with abstention. It is necessary to treat 112 asymptomatic patients with WPW to save one life over 10 years. Sensitivity analysis showed that 3 variables significantly impacted the decision to ablate: (1) complication of radiofrequency ablation, (2) success of radiofrequency ablation, and (3) sudden death in asymptomatic patients with WPW. CONCLUSIONS: This study provides a decision aid for treating asymptomatic patients with the WPW ECG pattern. Using the model and the population we tested, prophylactic catheter ablation is not yet ready for widespread clinical use.