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Aims The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF. Methods and results The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1(st) January 2020 and 30(th) November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 +/- 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001). Conclusions The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.

Abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel drug class that most cardiologists are becoming familiar with. By contrasting glucose reabsorption in the proximal convoluted tubule of the nephron, SGLT2 inhibition results in glycosuria with improved glycemic control. Although originally introduced as anti-diabetic medications, the cardiovascular effects of SGLT2i have progressively emerged, leading them to become one of the four pillars for the treatment of heart failure with reduced ejection fraction (HFrEF) according to the 2021 guidelines from the European Society of Cardiology. Also, two recent randomized trials have demonstrated SGLT2i as the first compounds with proven prognostic impact in heart failure with preserved ejection fraction (HFpEF), setting a milestone in the treatment for this condition. While the exact pathogenic mechanisms mediating the substantial reduction in cardiovascular death and heart failure (HF) hospitalizations are still controversial, there is growing clinical evidence on the efficacy and safety of SGLT2i in various subsets of patients with HF. As known, heart failure is a complex and heterogeneous clinical syndrome with a magnitude of phenotypes and a variety of underlying hemodynamic and physiological aspects which cannot be fully incorporated into the traditional left ventricular ejection fraction based classification adopted in clinical trials. The aim of this review is to provide an overview of the cardiovascular benefits and indications of SGLT2i across different HF patterns and to highlight current gaps in knowledge that should be addressed by future research.

Background GLP1-receptor agonists (GLP1-ra) are recently developed anti-diabetic drugs which have shown promising results in phase-3 cardiovascular (CV) outcomes trials in diabetic patients, demonstrating a reduction in major adverse cardiovascular events (MACE) and, possibly, in heart failure (HF) hospitalizations. However, whether these medications improve such outcomes in patients with a history of HF remains unknown. Methods All randomized, placebo-controlled trials of GLP1-ra (and predefined/post-hoc analysis) reporting CV outcomes stratified by HF history were searched in Pubmed from inception to August 31st, 2022. The primary outcome was HF hospitalizations. Secondary outcomes included MACE, CV death and a composite of HF hospitalization and CV death. The analysis was performed after stratifying for HF history. Odds-ratio (OR) and 95% confidence interval (CIs) were used as effect estimated and calculated via a random-effects model. P for interaction between subgroups were calculated via meta-regression analysis and a level of p Results Data from 6 trials and a total of 40300 patients (n=20127 GLP1-ra group, n=20173 placebo group) were included. GLP1-ra reduced HF hospitalizations in patients without HF history (OR 0.71, 95% CI 0.51-0.99) but had neutral effect on those with previous HF (OR 1.04, 95% CI 0.88–1.22, p-interaction=0.089). CV death was also reduced by intervention only in the group without history of HF (OR 0.81, 95% CI 0.71–0.92), as well as the composite of HF hospitalizations and CV death (OR 0.80, 95% CI 0.72–0.90). Indeed, no difference between treatment arms was found in the HF group for CV death (OR 0.99, 95% CI 0.82–1.18, p-interaction=0.18) and the composite of HF hospitalization or CV death (OR 1.02 95%CI 0.89–1.18, p-interaction=0.073). MACE reduction was similar in patients with (OR 0.87 95% CI 0.72–1.06) and without HF history (OR 0.84 95% CI 0.76–0.93, p-interaction = 0.75). Conclusion GLP1-ra do not reduce HF hospitalization and CV death in patients with history of HF, as the benefit on cardiovascular outcomes provided by this anti-diabetic class of drugs seems to be mainly limited to patients without HF history. Future studies focused on HF patients are needed to confirm such findings and clarify the limited efficacy of GLP1-ra in this relevant group of patients.

Aims Cardiovascular sequelae may occur in patients recovered from COVID-19. Recent studies have detected a considerable incidence of subclinical myocardial dysfunction – assessed with speckle-tracking echocardiography – and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. Methods and Results We prospectively followed-up 110 patients hospitalized at our Institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 6-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization and all-cause mortality. A subclinical myocardial dysfunction – defined as an impairment of left ventricular global longitudinal strain (≥ -18%) - was identified at 6-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (AUC: 0.73) and resulted a strong independent predictor of extended MACE in a multivariate regression analysis (OR 9.29, 95%CI 2.20–39.3, p=0.002). Long-COVID condition was not associated with a worse long-term prognosis, instead. Conclusion In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one third of the whole population at 6-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimise the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has not prognostic relevance.

Introduction Shark fin sign, also known as triangular QRS-ST-T waveform (TW), is characterized by a giant R wave (amplitude ≥ 1 mV) resulting from the fusion of the QRS complex, the ST-segment and the T wave and showing triangular morphology. TW pattern is quite uncommon and reveals a life-threatening condition that needs aggressive management. Early recognition is important to prevent acute complications such as ventricular arrhythmias and cardiogenic shock. Case presentation A 45-years old black man with history of arterial hypertension presented with out-of-hospital cardiac arrest (OHCA) at his workplace. Extracorporeal cardiopulmonary resuscitation started immediately and return of spontaneous circulation occurred after 11 minutes and 2 DC shocks. Then he was transferred to our emergency department (ED). At arrival he was hemodynamically stable, ECG showed atrial fibrillation without any repolarization abnormalities and echocardiogram revealed left ventricular hypertrophy (IVS 12mm, PW 12mm) and normal biventricular function. Normal electrolytes and high-sensitivity troponin level of 14 (n.v. 0.01-19.8 ng/L) were found at the blood test. Sedation in the ED was needed due to psychomotor agitation. He was then transferred to the CCU where spontaneous cardioversion to sinus rhythm occurred, and no additional arrhythmias were noted at continuous ECG monitoring. After ten hours, while the patient was still under sedation, ECG monitoring revealed a progressive QRS-ST segment elevation in inferior leads up to a triangular QRS-ST-T giant waveform (“Shark fin sign”), without hemodynamic deterioration. After approximately 3 minutes the ECG showed a progressive and complete regression to a normal waveform. An emergent beside echocardiogram demonstrated inferior wall hypokinesia, but normal pump function. The episode repeated 5 more times in the following hour, waiting for cath lab personnel. Coronary angiography revealed a sub-occlusive mid RCA stenosis without any thrombotic lesion. Percutaneous coronary intervention (PCI) with the implantation of one drug eluting stent (DES) was performed. After the procedure the patient was hemodynamically and electrically stable. ECG did not show any other abnormality and no episodes of recurrent ST-elevation occurred. Sedation was suspended and no focal neurological deficits were noted. Discussion Shark fin sign is the expression of abrupt total deprivation of blood flow in large areas of myocardium that cause massive slowing of transmural electrical conduction. These electrical differences may be at the base of the triangular R waves and predispose to VF induction and cardiogenic shock. This sign is very rare, with an annual incidence of 0.7% in patients admitted for STEMI, and in most of the cases is described in the occlusion of the LAD. In our case we assisted to transient but repetitive inferior triangular ST-elevation with complete regression to normal ECG. The coronary angiogram showed non-obstructive lesion of the RCA. This phenomenon was probably the expression of RCA's plaque coronary vasospasm that caused the ECG shark fin sign and cardiac arrest. Conclusion Shark fin electrocardiographic waveform is an uncommon pattern of STEMI and may be the expression of thrombotic coronary occlusion as well as massive coronary vasospasm. This sign correlates with high risk of cardiogenic shock, electrical instability, and cardiac arrest, thus requiring prompt and aggressive management.

Introduction Mitral regurgitation (MR) and tricuspid regurgitation (TR) are an established cause of morbidity and mortality in heart failure (HF) patients. The development of successful transcatheter therapies for mitral and tricuspid diseases have opened new therapeutic opportunities, in addition to guideline-directed medical therapy (GDMT) for HF. However, an accurate evaluation of the mechanisms of valve regurgitation is key to tailor the best treatment for each patient. This study aims at evaluating the prevalence and underlying mechanisms of at least moderate-to-severe (≥3+/4+) MR and/or TR in a cohort of HF outpatients. Methods We retrospectively analyzed the medical records of 1260 outpatients evaluated by our HF Unit between January 2020 and June 2021. All patients with echocardiographic evidence of at least moderate-to-severe MR and/or TR were included in the registry and a thorough review of echocardiographic images and collection of clinical data were also performed. Results Of the 1260 analyzed patients, 173 (13.7%) presented with at least moderate-to-severe MR and/or TR and were included in the registry. The mean age was 80±7 years and median ejection fraction was 45% (IQR 33; 55%) and 77 (45%) had HF of ischemic etiology. All patients were treated with maximal tolerated doses of GDMT and, when appropriate, with devices and myocardial revascularization. At least moderate-to-severe MR and TR was observed in 7.3% (92/1260) and 9.3% (117/1260) patients, respectively. Patients with significant isolated MR were 56 (4.4%), with isolated TR were 81 (6.4%), while with both significant MR and TR were 36 (2.8%). Among patients with significant MR, 54% (50/92) had functional valvular defect, of whom 82% (41/50) had a ventricular etiology (18/41 with asymmetric tethering), while the 18%(9/50) an atrial one (3/9 with atriogenic tethering). Among patients with significant TR, 72.6% (85/117) had functional valvular defect, of whom 35.3% (30/85) had a ventricular etiology while 64.7% (55/85) presented with an atrial one. Conclusion Despite optimized GDMT, the prevalence of patients presenting with significant MR and TR was considerably high in our ambulatory HF population. This registry is the first study to comprehensively detail the mechanisms of atrioventricular valve regurgitations in a wide cohort of HF outpatients. Further studies are needed to assess the reasons for a potential undertreatment and to identify the patients who would benefit the most from the percutaneous correction of their valvular defects.

Background Loop diuretics are the cornerstone of acutely decompensated heart failure (ADHF) treatment, but evidences on doses and administration modalities are still lacking. Veena S. et al have recently validated the Natriuretic Response Prediction Equation and applied it with the Yale Diuretic Protocol (YDP) in a clinical implementation cohort demonstrating its safety. Objectives Our purpose is to test the applicability and safety of YDP for titration of diuretic therapy in a real–world in–hospital setting, as compared to standard diuretic therapy. METHODS From 15th September 2021 patients hospitalized with ADHF, almost one sign of congestion and need of i.v. diuretics were enrolled. Patients with active bleeding, hematocrit Results Thirty patients were included. Median age was 76.4 [IQR 68.3; 82.7] years old; median EF and glomerular filtration rate were 40% [IQR 30; 55] and 57.2 ml/min/m2 [IQR 44.9; 79.9], respectively. Nineteen (63.3%) patients were on chronic loop diuretic treatment. Ten (33.3%) patients were treated according to YDP. Main results are shown in the Table attached. YDP patients were younger (p = 0.02) and received shorter treatment with i.v. diuretics (YDP 36 [IQR 27; 48] hours, controls 48 [IQRS 38; 88] hours; p = 0.03). No differences in terms of total diuresis, weight loss at the end of i.v. diuretic therapy and length of hospitalization were shown. YDP patients experienced significant lower increase in creatinine during i.v. diuretic therapy (p = 0.02). The incidence of adverse events was comparable between groups, with equal hypotension rate (10%), and similar plasma levels of electrolytes at the end of i.v. diuretic therapy; YDP patients required less potassium supplementation. Reasons for i.v. diuretic therapy suspension were comparable between groups; 7 (70%) YDP patients concluded i.v. diuretic therapy for satisfactory decongestion, while only one patient because of hypotension and none because of worsening of renal function. Conclusion In our reality the YDP appeared to be applicable, safe and comparable to the standard i.v. diuretic therapy in terms of in–hospital outcomes. These preliminary results need to be confirmed in a larger cohort and longer term outcomes still need to be explored.

Introduction Mitral regurgitation (MR) and tricuspid regurgitation (TR) are a known cause of morbidity and mortality in heart failure (HF) patients. Maximal up–titration of guideline–directed medical therapy (GDMT) for HF may not be enough to reduce the severity of the valve’s incompetence and patients’ symptoms. The development and successful results of transcatheter therapies for mitral/tricuspid disease have opened new therapeutic opportunities when surgery is not feasible. Accurate valve regurgitation’s mechanisms evaluation is essential to choose the best treatment option. This study aims at evaluating the prevalence and underlying mechanisms of at least moderate–to–severe (≥3+/4+) MR and/or TR in a cohort of HF outpatients. Methods We retrospectively analyzed the medical records of 1260 outpatients evaluated by our HF unit between January 2020 and June 2021. All patients with echocardiographic evidence of ≥ 3+/4+ MR and/or TR were included (treated ones were excluded), and a thorough echocardiographic images review was conducted. A full collection of patients’ clinical, laboratory and therapy regimens details was performed as well. Results Of the 1260 analyzed patients, 173 (13.7%) exhibited ≥3+/4+ MR and/or TR and were included in the registry. Table 1 shows the main clinical/echocardiographic characteristics. Mean age was 80±7 years, median ejection fraction was 45% (IQR=33–55). All patients were treated with maximal tolerated doses of GDMT and, if appropriate, with cardiac devices/myocardial revascularization. ≥3+/4+ MR and/or TR was observed in 92 (7.3%) and 117 (9.3%) patients, respectively. Patients with isolated significant MR were 56 (4.4%), with isolated significant TR were 81 (6.4%); the remaining 36 (2.8%) had both MR/TR. Among patients with significant MR, 50 (54%) had functional/secondary valvular defect (details in Figure 2): the majority (41,82%) presented a ventricular etiology (asymmetric tethering in 18/41) while 9 (18%) an atrial one (atriogenic tethering in 3/9). Conclusion Despite optimized GDMT, the prevalence of patients with hemodynamically significant valvular defects was considerably high in our HF population. This is the first registry to comprehensively detail atrioventricular valve regurgitations’ mechanisms in a wide real–life cohort of HF outpatients. Further studies are needed to identify reasons for potential undertreatment and patients who would benefit the most from percutaneous correction of their valvular defects.