Atrial Fibrillation, Atrial Myopathy, and Thromboembolism: The Additive Value of Echocardiography and Possible New Horizons for Risk Stratification.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, and it is associated with increased stroke and dementia risk. While the established paradigm attributes these complications to blood stasis within the atria and subsequent thrombus formation with cerebral embolization, recent evidence suggests that atrial myopathy (AM) may play a key role. AM is characterized by structural and functional abnormalities of the atria, and can occur with or without AF. Moving beyond classifications based solely on episode duration, the 4S-AF characterization has offered a more comprehensive approach, incorporating patient's stroke risk, symptom severity, AF burden, and substrate assessment (including AM) for tailored treatment decisions. The "ABC" pathway emphasizes anticoagulation, symptom control, and cardiovascular risk modification and emerging evidence suggests broader benefits of early rhythm control strategies, potentially reducing stroke and dementia risk and improving clinical outcomes. However, a better integration of AM assessment into the current framework holds promise for further personalizing AF management and optimizing patient outcomes. This review explores the emerging concept of AM and its potential role as a risk factor for stroke and dementia and in AF patients' management strategies, highlighting the limitations of current risk stratification methods, like the CHA2DS2-VASc score. Echocardiography, particularly left atrial (LA) strain analysis, has shown to be a promising non-invasive tool for AM evaluation and recent studies suggest that LA strain analysis may be a more sensitive risk stratifier for thromboembolic events than AF itself, with some studies showing a stronger association between LA strain and thromboembolic events compared to traditional risk factors. Integrating it into routine clinical practice could improve patient management and targeted therapies for AF and potentially other thromboembolic events. Future studies are needed to explore the efficacy and safety of anticoagulation in AM patients with and without AF and to refine the diagnostic criteria for AM.

Stress echocardiography in heart failure patients: additive value and caveats.

Heart failure (HF) is a clinical syndrome characterized by well-defined signs and symptoms due to structural and/or myocardial functional impairment, resulting in raised intracardiac pressures and/or inadequate cardiac stroke volume at rest or during exercise. This could derive from direct ischemic myocardial injury or other chronic pathological conditions, including valvular heart disease (VHD) and primary myocardial disease. Early identification of HF etiology is essential for accurate diagnosis and initiation of early and appropriate treatment. Thus, the presence of accurate means for early diagnosis of HF symptoms or subclinical phases is fundamental, among which echocardiography being the first line diagnostic investigation. Echocardiography could be performed at rest, to identify overt structural and functional abnormalities or during physical or pharmacological stress, in order to elicit subclinical myocardial function impairment e.g. wall motion abnormalities and raised ventricular filling pressures. Beyond diagnosis of ischemic heart disease, stress echocardiography (SE) has recently shown its unique value for the evaluation of diastolic heart failure, VHD, non-ischemic cardiomyopathies and pulmonary hypertension, with recommendations from international societies in several clinical settings. All these features make SE an important additional tool, not only for diagnostic assessment, but also for prognostic stratification and therapeutic management of patients with HF. In this review, the unique value of SE in the evaluation of HF patients will be described, with the objective to provide an overview of the validated methods for each setting, particularly for HF management.

Usefulness of Combined Ultrasound Assessment of E/e' Ratio, Pulmonary Pressure, and Cava Vein Status in Patients With Acute Heart Failure.

Congestion is poorly investigated by ultrasound scans during acute heart failure (AHF) and systematic studies evaluating ultrasound indexes of cardiac pulmonary and systemic congestion during early hospital admission are lacking. We aimed to investigate the prevalence of ultrasound cardiac pulmonary and systemic congestion in a consecutive cohort of hospitalized patients with AHF, analyzing the relevance of each ultrasound congestion component (cardiac, pulmonary, and systemic) in predicting the risk of death and rehospitalization. This is a prospective research study of a single center that evaluates patients with an AHF diagnosis who are divided according to the left ventricular ejection fraction in patients with heart failure with preserved ejection fraction or reduced ejection fraction. We performed a complete bedside echocardiography and lung ultrasound analyses within the first 24 hours of hospital admission. The ultrasound congestion score was preliminarily established by measuring the following parameters: cardiac congestion, which was defined as the contemporary presence of E/e' >15 and pulmonary systolic pressure >35 mm Hg and the pulmonary congestion, defined as the total B-line number >25 at the lung ultrasound performed in 8 chest sites; moreover, the systemic congestion was defined if the inferior vena cava (IVC) was >21 mm and if it was associated with a reduced inspiratory collapse >50%. We thoroughly assessed 230 patients and evaluated their results. Of these patients, 135 had heart failure with reduced ejection fraction and there were 95 patients with heart failure with preserved ejection fraction; 122 patients experienced adverse events during the 180-day follow-up. The receiver operating characteristic curve analysis showed that the tricuspid annular peak systolic excursion (TAPSE) (area under the curve [AUC] 0.34 [0.26 to 0.41], p <0.001), E/e' (AUC 0.62 [0.54 to 0.69], p = 0.003), and IVC (AUC 0.70 [0.63 to 0.77], p <0.001) were all significantly related to poor prognosis detection. The univariate Cox regression analysis revealed that cardiac congestion in terms of E/e' and pulmonary systolic pressure (hazard ratio [HR] 1.49 [1.02 to 2.17], p = 0.037), TAPSE (HR 0.90 [0.85 to 0.94], p <0.001), and systemic congestion (HR 2.64 [1.53 to 4.56], p <0.001) were all significantly related to the 180-day outcome. After adjustment for potential confounders, only TAPSE (HR 0.92 [0.88 to 0.98], p = 0.005) and IVC (HR 1.92 [1.07 to 3.46], p = 0.029) confirmed their prognostic role. The multivariable analysis of multiple congestion levels in terms of systemic plus cardiac (HR 1.54 [1.05 to 2.25], p = 0.03), systemic plus pulmonary (HR 2.26 [1.47 to 3.47], p <0.001), and all 3 congestion features (HR 1.53 [1.06 to 2.23], p = 0.02) revealed an incremental prognostic role for each additional determinant. In conclusion, among the ultrasound indexes of congestion, IVC and TAPSE are related to adverse prognosis, and the addition of pulmonary and cardiac congestion indexes increases the risk prediction accuracy. Our data confirmed that right ventricular dysfunction and systemic congestion are the most powerful predictive factors in AHF.

Different right ventricular dysfunction and pulmonary coupling in acute heart failure according to the left ventricular ejection fraction.

BACKGROUND: Right ventricular (RV) dysfunction and pulmonary uncoupling are two acknowledged features associated with poor outcome, however few data defined RV adaptation across the different left ventricular ejection fraction (EF) cut-off. Additionally, less data are reported in patients with acute heart failure (AHF). AIMS: The aim of present study was to analyse RV function in AHF patients presenting with either reduced or preserved EF. METHODS: This is a multi-center observational study including 380 patients affected by AHF: 235 had AHF with reduced EF (AHFrEF) and 145 had AHF with preserved EF (AHFpEF). Pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), S' wave velocity, and the RV end-diastolic diameter (RVEDD) were measured by echocardiography. TAPSE/PASP and S'/PASP ratios were calculated as non-invasive surrogates of RV-pulmonary arterial coupling. RESULTS: Factors associated with poor outcome were higher values of PASP (45 [40-55] mmHg vs 40 [35-46] mmHg; p < 0.001), RVEDD (44 [38-47] mm vs 37 [35-42] mm; p < 0.001), lower TAPSE values (17 [15-20] mm vs 20 [18-22] mm; p < 0.001) and S' wave (10 [8-12] cm/s vs 11 [10-13] cm/s; p < 0.001), reduced TAPSE/PASP (0.37 [0.29-0.47] vs 0.50 [0.40-0.60]; p < 0.001) and S'/PASP ratios (0.22 [0.18-0.28] vs 0.28 [0.22-0.34]; p < 0.001). However, the prognostic parameters differed according to the LVEF value: in AHFpEF S'/PASP between 0.22 and 0.29 and > 0.29 demonstrated a protective prognostic value (Respectively HR 0.29 (0.16-0.53), p < 0.001 and HR 0.22 [0.12-0.42], p < 0.001). Conversely, in AHFrEF, TAPSE <16 mm (HR 2.59 [1.67-4.03], p < 0.001), ICV > 21 mm (HR 1.17 [1.17-1.28], p = 0.001) and TAPSE/PASP <0.49 HR 1.92 [1.10-3.37], p = 0.023) were related to adverse outcome. CONCLUSIONS: RV adaptation and RV pulmonary coupling differ in AHF according to the level of LVEF. S' wave, and S'/PASP are associated with adverse outcome in patients with preserved EF; reduced TAPSE and TAPSE/PASP are better prognostic predictors in patients with reduced EF.

Vericiguat in Heart Failure: Characteristics, Scientific Evidence and Potential Clinical Applications.

Despite recent advances in heart failure (HF) management, the risk of death and hospitalizations remains high in the long term. HF is characterized by endothelial dysfunction, inflammation and increased oxidative stress, due to a reduction in the activity of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway. All these factors contribute to direct damage at the myocardial, vascular and renal level. Vericiguat restores the deficiency in this signaling pathway, through stimulation and activation of sGC, aiming to increase cGMP levels, with a reduction in HF-related oxidative stress and endothelial dysfunction. Two main clinical trials were developed in this setting: the SOCRATES-REDUCED phase II study and the VICTORIA phase III study. They found that vericiguat is safe, well tolerated and effective with an absolute event-rate reduction in patients affected by HF with reduced ejection fraction (HFrEF) and recent cardiac decompensation. In patients with HF with preserved ejection fraction (HfpEF), the SOCRATES-PRESERVED trial demonstrated an improvement in quality of life and health status, but the proven beneficial effects with vericiguat are still limited. Further studies are needed to correctly define the role of this drug in heart failure syndromes. Our paper reviews the potential applications and pharmacological characteristics of vericiguat in HFrEF and HFpEF.

Patients with cardiac amyloidosis have a greater neurohormonal activation than those with non-amyloidotic heart failure.

BACKGROUND: Neurohormonal activation has never been investigated in patients with cardiac amyloidosis (CA). METHODS: Forty-seven patients with amyloid light-chain (AL)-CA and 61 with transthyretin (ATTR)-CA were matched to non-amyloidotic heart failure (HF) patients based on age, sex, left ventricular ejection fraction ranges, renal function and HF therapies. N-terminal pro-B-type natriuretic peptide (NT-proBNP), norepinephrine and renin were dosed. The primary and secondary endpoints were 1-year cardiovascular death or HF hospitalisation, and 5-year cardiovascular death, respectively. RESULTS: Patients with AL-CA had a 10-fold higher NT-proBNP than HF patients (6548 ng/L [2059-15,097] vs. 692 [243-2241], p < 0.001), and slightly higher norepinephrine (595 ng/L [383-869] vs. 416 [250-693], p = 0.047). Patients with ATTR-CA had higher NT-proBNP (3984 ng/L [2275-9505] vs. 1751 [470-4768], p = 0.006), norepinephrine (552 ng/L [344-855] vs. 441 [323-601], p = 0.020), and renin (14 mU/L [8-80] vs. 10 [4-34], p = 0.017). Patients with AL- or ATTR-CA had more often 2 or 3 neurohormones above the corresponding upper reference limits than matched HF patients. NT-proBNP and aldosterone were univariate predictors of the primary endpoint in patients with ATTR-CA, but not in matched controls. NT-proBNP and renin predicted the secondary endpoint in patients with AL-CA, but not in matched controls. CONCLUSIONS: Patients with CA display a neurohormonal activation, with some prognostic significance.