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 haemoglobin and serum markers of iron deficiency in people with cardiovascular disease.

BACKGROUND: The prevalence of anaemia and iron deficiency and their prognostic association with cardiovascular disease have rarely been explored at population level. METHODS: National Health Service records of the Greater Glasgow region for patients aged ≥50 years with a broad range of cardiovascular diagnoses were obtained. During 2013/14, prevalent disease was identified and results of investigations collated. Anaemia was defined as haemoglobin <13 g/dL for men or <12 g/dL for women. Incident heart failure, cancer and death between 2015 and 2018 were identified. RESULTS: The 2013/14 dataset comprised 197 152 patients, including 14 335 (7%) with heart failure. Most (78%) patients had haemoglobin measured, especially those with heart failure (90%). Of those tested, anaemia was common both in patients without (29%) and with heart failure (prevalent cases in 2013/14: 46%; incident cases during 2013/14: 57%). Ferritin was usually measured only when haemoglobin was markedly depressed; transferrin saturation (TSAT) even less often. Incidence rates for heart failure and cancer during 2015-18 were inversely related to nadir haemoglobin in 2013/14. A haemoglobin of 13-15 g/dL for women and 14-16 g/dL for men was associated with the lowest mortality. Low ferritin was associated with a better prognosis and low TSAT with a worse prognosis. CONCLUSION: In patients with a broad range of cardiovascular disorders, haemoglobin is often measured but, unless anaemia is severe, markers of iron deficiency are usually not. Low haemoglobin and TSAT, but not low ferritin, are associated with a worse prognosis. The nadir of risk occurs at haemoglobin 1-3 g/dL above the WHO definition of anaemia.

The incremental value of multi-organ assessment of congestion using ultrasound in outpatients with heart failure.

AIMS: We investigated the prevalence and clinical value of assessing multi-organ congestion by ultrasound in heart failure (HF) outpatients. METHODS AND RESULTS: Ultrasound congestion was defined as inferior vena cava of ≥21 mm, highest tertile of lung B-lines, or discontinuous renal venous flow. Associations with clinical characteristics and prognosis were explored. We enrolled 310 HF patients [median age: 77 years, median NT-proBNP: 1037 ng/L, 51% with a left ventricular ejection fraction (LVEF) <50%], and 101 patients without HF. There were no clinical signs of congestion in 224 (72%) patients with HF, of whom 95 (42%) had at least one sign of congestion by ultrasound (P < 0.0001). HF patients with ≥2 ultrasound signs were older, and had greater neurohormonal activation, lower urinary sodium concentration, and larger left atria despite similar LVEF. During a median follow-up of 13 (interquartile range: 6-15) months, 77 patients (19%) died or were hospitalized for HF. HF patients without ultrasound evidence of congestion had a similar outcome to patients without HF [reference; hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.86-1.35], while those with ≥2 ultrasound signs had the worst outcome (HR 26.7, 95% CI 12.4-63.6), even after adjusting for multiple clinical variables and NT-proBNP. Adding multi-organ assessment of congestion by ultrasound to a clinical model, including NT-proBNP, provided a net reclassification improvement of 28% (P = 0.03). CONCLUSION: Simultaneous assessment of pulmonary, venous, and kidney congestion by ultrasound is feasible, fast, and identifies a high prevalence of sub-clinical congestion associated with poor outcomes.

Remote laser-speckle sensing of heart sounds for health assessment and biometric identification.

Assessment of heart sounds is the cornerstone of cardiac examination, but it requires a stethoscope, skills and experience, and a direct contact with the patient. We developed a contactless, machine-learning assisted method for heart-sound identification and quantification based on the remote measurement of the reflected laser speckle from the neck skin surface in healthy individuals. We compare the performance of this method to standard digital stethoscope recordings on an example task of heart-beat sound biometric identification. We show that our method outperforms the stethoscope even allowing identification on the test data taken on different days. This method might allow development of devices for remote monitoring of cardiovascular health in different settings.

Dynamic risk stratification using Markov chain modelling in patients with chronic heart failure.

AIMS: Risk changes with the progression of disease and the impact of treatment. We developed a dynamic risk stratification Markov chain model using artificial intelligence in patients with chronic heart failure (CHF). METHODS AND RESULTS: We described the pattern of behaviour among 7496 consecutive patients assessed for suspected HF. The following mutually exclusive health states were defined and assessed every 4 months: death, hospitalization, outpatient visit, no event, and leaving the service altogether (defined as no event at any point following assessment). The observed figures at the first transition (4 months) weres 427 (6%), 1559 (21%), 2254 (30%), 1414 (19%), and 1842 (25%), respectively. The probabilities derived from the first two transitions (i.e. from baseline to 4 months and from 4 to 8 months) were used to construct the model. An example of the model's prediction is that at cycle 4, the cumulative probability of death was 14%; leaving the system, 37%; being hospitalized between 12 and 16 months, 10%; having an outpatient visit, 8%; and having no event, 31%. The corresponding observed figures were 14%, 41%, 10%, 15%, and 21%, respectively. The model predicted that during the first 2 years, a patient had a probability of dying of 0.19, and the observed value was 0.18. CONCLUSIONS: A model derived from the first 8 months of follow-up is strongly predictive of future events in a population of patients with chronic heart failure. The course of CHF is more linear than is commonly supposed, and thus more predictable.

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).

Congestion in Patients with Advanced Heart Failure: Assessment and Treatment.

Heart failure (HF) is characterized by frequent hospital admissions due to acute decompensation and shortened life span with a progressive clinical course leading to an advanced stage where traditional therapies become ineffective. Due to aging of the population and improved therapies, only a small of proportion of patients with advanced HF are candidates for surgical treatments, such as mechanical circulatory support or heart transplantation. In most cases, prompt identification and management of congestion is paramount to improving symptoms and quality of life and avoiding progression to severe multiorgan dysfunction and death.

Assessment of Phasic Changes of Vascular Size by Automated Edge Tracking-State of the Art and Clinical Perspectives.

Assessment of vascular size and of its phasic changes by ultrasound is important for the management of many clinical conditions. For example, a dilated and stiff inferior vena cava reflects increased intravascular volume and identifies patients with heart failure at greater risk of an early death. However, lack of standardization and sub-optimal intra- and inter- operator reproducibility limit the use of these techniques. To overcome these limitations, we developed two image-processing algorithms that quantify phasic vascular deformation by tracking wall movements, either in long or in short axis. Prospective studies will verify the clinical applicability and utility of these methods in different settings, vessels and medical conditions.