Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. OBJECTIVES: This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). METHODS: This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. RESULTS: Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. CONCLUSIONS: This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Biventricular or Conduction System Pacing for Cardiac Resynchronization Therapy: A Strategy for Cardiac Resynchronization Based on a Hybrid Approach.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently, conduction system pacing (CSP) has been proposed as an alternative in case of BiVP failure. The aim of this study is to define an algorithm to choose between BiVP and CSP resynchronization using the interventricular conduction delays (IVCD) as a guide. METHODS: Consecutive patients from January 2018 to December 2020 with an indication for CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). A treatment algorithm based on IVCD was used to decide whether to leave the left ventricular (LV) lead to perform BiVP or pull it out and perform CSP. Outcomes from the DRG group were compared to a historical cohort of CRT patients who underwent CRT procedures between January 2016 and December 2017 (resynchronization standard guide group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or HF event at 1 year after the date of intervention. RESULTS: The study population consisted of 292 patients, of which 160 (54.8%) were in the DRG and 132 (45.2%) in the SRG. In the DRG, 41 of 160 patients underwent CSP based on the treatment algorithm (25.6%). The primary endpoint was significantly higher in the SRG (48/132, 36.4%) compared to the DRG (35/160, 21.8%) (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.12-2.65; p = 0.013). CONCLUSIONS: A treatment algorithm based on IVCD shifted one patient out of every four from BiVP to CSP, with consequent reduction in the primary endpoint after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP.

Left ventricular assist device in cardiac amyloidosis: friend or foe?

The prevalence of cardiac amyloidosis has progressively increased over the last years, being recognized as a significant cause of heart failure. In fact, the management of advanced heart failure is a cornerstone treatment of amyloid cardiomyopathy due to the frequent delay in its diagnosis. Left ventricular assist devices (LVADs) have been gaining importance in the scenario of end-stage heart failure, representing an alternative to heart transplant. However, only few studies have investigated the role of LVAD in restrictive cardiomyopathies such as cardiac amyloidosis, since there are several problems to consider. In fact, both anatomical factors and the restrictive physiology of this condition make LVAD implant a relevant challenge in this subset of patients. Furthermore, due to the systemic involvement of amyloidosis, several factors have to be considered after LVAD implant, such as an increased risk of bleeding and right ventricular failure. This review attempts to summarize the current evidence of LVAD in cardiac amyloidosis, especially focusing on the challenges that this cardiomyopathy imposes both to the implant and to its management thereafter.

Prediction of congestive state in acute and chronic heart failure: The association between NT-proBNP and left atrial strain and its prognostic value.

BACKGROUND: The relief of congestion is crucial to improve heart failure (HF) patient's quality of life and prognosis. N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a well-known marker of congestion, although with limited specificity. Peak atrial longitudinal strain (PALS) by speckle tracking echocardiography (STE) is an index of intracardiac pressure and HF prognosis. We aimed to determine the association between NT-proBNP and PALS and its prognostic implications in patients with HF. METHODS: Patients hospitalized for de-novo or recurrent HF and outpatients with chronic HF were included in this retrospective study. Patients with missing data, previous cardiac surgery, non-feasible STE were excluded. Clinical, laboratory and echocardiographic data were collected. STE was performed on echocardiographic records. Primary endpoint was a combination of all-cause death and HF hospitalization. RESULTS: Overall, 388 patients were included (172 acute HF, 216 chronic HF, mean age = 65 ± 12 years, 37% female). Mean LV ejection fraction = 31 ± 9%. Global PALS showed a significant inverse correlation with NT-proBNP in acute and chronic HF (all p < 0.001). During a median follow-up of 4 years, 180 patients reached the combined endpoint. NT-proBNP (AUC = 0.87) and global PALS (AUC = 0.82) were good predictors of the combined endpoint. Global PALS was the only independent predictor of the combined endpoint. Optimal risk stratification for the composite endpoint was provided combining PALS ≤15% and NTproBNP ≥874.5 ng/l. CONCLUSIONS: Global PALS is associated with NT-proBNP in acute and chronic HF and may be used as additional index of congestion to optimize therapeutic management. The combination of global PALS and NT-proBNP could enhance the prognostic stratification of HF.

Bedside Ultrasound for Hemodynamic Monitoring in Cardiac Intensive Care Unit.

Thanks to the advances in medical therapy and assist devices, the management of patients hospitalized in cardiac intensive care unit (CICU) is becoming increasingly challenging. In fact, Patients in the cardiac intensive care unit are frequently characterized by dynamic and variable diseases, which may evolve into several clinical phenotypes based on underlying etiology and its complexity. Therefore, the use of noninvasive tools in order to provide a personalized approach to these patients, according to their phenotype, may help to optimize the therapeutic strategies towards the underlying etiology. Echocardiography is the most reliable and feasible bedside method to assess cardiac function repeatedly, assisting clinicians not only in characterizing hemodynamic disorders, but also in helping to guide interventions and monitor response to therapies. Beyond basic echocardiographic parameters, its application has been expanded with the introduction of new tools such as lung ultrasound (LUS), the Venous Excess UltraSound (VexUS) grading system, and the assessment of pulmonary hypertension, which is fundamental to guide oxygen therapy. The aim of this review is to provide an overview on the current knowledge about the pathophysiology and echocardiographic evaluation of perfusion and congestion in patients in CICU, and to provide practical indications for the use of echocardiography across clinical phenotypes and new applications in CICU.

Non-invasive assessment of acute heart failure by Stevenson classification: Does echocardiographic examination recognize different phenotypes?

Background: Acute heart failure (AHF) presentation is universally classified in relation to the presence or absence of congestion and the peripheral perfusion condition according to the Stevenson diagram. We sought to evaluate a relationship existing between clinical assessment and echocardiographic evaluation in patients with AHF. Materials and methods: This is a retrospective blinded multicenter analysis assessing both clinical and echocardiographic analyses during the early hospital admission for AHF. Patients were categorized into four groups according to the Stevenson presentation: group A (warm and dry), group B (cold and dry), group C (warm and wet), and group D (cold and wet). Echocardiographic evaluation was executed within 12 h from the first clinical evaluation. The following parameters were measured: left ventricular (LV) volumes, LV ejection fraction (LVEF); pattern Doppler by E/e1 ratio, pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), and inferior cave vein diameter (ICV). Results: We studied 208 patients, 10 in group A, 16 in group B, 153 in group C, and 29 in group D. Median age of our sample was 81 [69-86] years and the patients enrolled were mainly men (66.8%). Patients in groups C and A showed significant higher levels of systolic arterial pressures with respect to groups B and D (respectively, 130 [115-145] mmHg vs. 122 [119-130] mmHg vs. 92 [90-100] mmHg vs. 95 [90-100] mmHg, p < 0.001). Patients in groups A and C (warm) demonstrated significant higher values of LVEF with respect to patients in groups B and D (43 [34-49] vs. 42 [30-49] vs. 27 [15-31] vs. 30 [22-42]%, p < 0.001). Whereas group B experienced significant lower TAPSE values compared with other group (14 [12-17] mm vs. A: 17 [16-21] mm vs. C: 18 [14-20] mm vs. D: 16 [12-17] mm; p = 0.02). Finally, echocardiographic congestion score including PASP ≥ 40 mmHg, ICV ≥ 21, mm and E/e' > 14 did not differ among groups. Follow-up analysis showed an increased mortality rate in D group (HR 8.2 p < 0.04). Conclusion: The early Stevenson classification remains a simple and universally recognized approach for the detection of congestion and perfusion status. The combined clinical and echocardiographic assessment may be useful to better define the patients' profile.

Effects of Metolazone Administration on Congestion, Diuretic Response and Renal Function in Patients with Advanced Heart Failure.

BACKGROUND: Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a detrimental impact on prognosis and hospitalization. AIMS: This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed. METHODS: We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF < 40%) taking a mean furosemide amount of 250 ± 120 mg/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis/40 mg of furosemide. RESULTS: Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 ± 0.7 in Group F vs. 3 ± 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F; p = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 ± 1 in Group M vs. 3 ± 1 in Group F p > 0.05). Clinical congestion resolution was also associated with weight reduction (-6 ± 2 in Group M vs. -3 ± 1 kg in Group F, p < 0.05). Better DR response was observed in Group M compared to F (940 ± 149 mL/40 mgFUROSEMIDE/die vs. 541 ± 314 mL/40 mgFUROSEMIDE/die; p < 0.01), whereas median ΔNTproBNP remained similar between the two groups (-4819 ± 8718 in Group M vs. -3954 ± 5560 pg/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 ± 900 vs. 2050 ± 1120 mL p < 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%). CONCLUSIONS: Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF.

SiCILIA-Silicon Carbide Detectors for Intense Luminosity Investigations and Applications.

Silicon carbide (SiC) is a compound semiconductor, which is considered as a possible alternative to silicon for particles and photons detection. Its characteristics make it very promising for the next generation of nuclear and particle physics experiments at high beam luminosity. Silicon Carbide detectors for Intense Luminosity Investigations and Applications (SiCILIA) is a project starting as a collaboration between the Italian National Institute of Nuclear Physics (INFN) and IMM-CNR, aiming at the realization of innovative detection systems based on SiC. In this paper, we discuss the main features of silicon carbide as a material and its potential application in the field of particles and photons detectors, the project structure and the strategies used for the prototype realization, and the first results concerning prototype production and their performance.