Left Atrial Functional Remodeling in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan.

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.

The Evolving Phenotypes of Cardiovascular Disease during COVID-19 Pandemic.

COVID-19 pandemic has negatively impacted the management of patients with acute and chronic cardiovascular disease: acute coronary syndrome patients were often not timely reperfused, heart failure patients not adequately followed up and titrated, atrial arrhythmias not efficaciously treated and became chronic. New phenotypes of cardiovascular patients were more and more frequent during COVID-19 pandemic and are expected to be even more frequent in the next future in the new world shaped by the pandemic. We therefore aimed to briefly summarize the main changes in the phenotype of cardiovascular patients in the COVID-19 era, focusing on new clinical challenges and possible therapeutic options.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Optimizing Therapies in Heart Failure: The Role of Potassium Binders.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3-18% of HF patients from randomized controlled trials and over 25% of HF patients in the "real world" setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K+ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

Pharmacological Anti-Remodelling Effects of Disease-Modifying Drugs in Heart Failure with Reduced Ejection Fraction.

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and ß-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins.

Arrhythmic myocarditis in an adolescent male: A unique presentation of multi-organ inflammatory syndrome (MIS-C).

Although children with Covid-19 generally present with mild symptoms or are often asymptomatic, there is increasing recognition of a delayed multi-organ inflammatory syndrome (MIS-C) following SARS-CoV-2 infection. We report the case of MIS-C associated arrhythmic myocarditis which recovered after anti-inflammatory therapy and immunoglobulin infusion.

Incidence of cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors.

BACKGROUND: The introduction of imatinib and tyrosine kinase inhibitors as therapeutic strategy for Philadelphia chromosome-positive chronic myeloid leukaemia (CML) has represented an important step forward for treatment of this disease. The aim of this study was therefore to evaluate the incidence of cardiovascular adverse events (CVEs) in patients affected by CML treated with TKI in an observational prospective study. METHODS: All consecutive patients affected by CML and treated with TKI in our Institution were enrolled in the study from February 2005 to September 2018 with a clinical, laboratory and instrumental follow-up. RESULTS: Sixty-one consecutive patients were enrolled, 29 with imatinib, 15 with nilotinib, 11 with dasatinib, 3 with bosutinib and 3 with ponatinib. Neither patients in therapy with bosutinib nor with nilotinib had CVE during follow-up. Incidence rates per person/year were 0 for bosutinib and nilotinib, 0.15 for dasatinib, 0.19 for imatinib and 1.69 for ponatinib (Log Rank p < 0.05); differences in terms of incidence of adverse outcomes remained significant also after multivariate correction. CONCLUSIONS: In patients with CML treated with TKIs, therapy with ponatinib was associated with a higher risk of CVE than other TKIs. The lowest incidence of CVE was associated with bosutinib and nilotinib.

Switch to SGLT2 Inhibitors and Improved Endothelial Function in Diabetic Patients with Chronic Heart Failure.

PURPOSE: The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. METHODS: Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. RESULTS: Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001). CONCLUSIONS: Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Predictors of right ventricular function improvement with sacubitril/valsartan in a real-life population of patients with chronic heart failure.

BACKGROUND: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. METHODS: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II-III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. RESULTS: After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S' (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV-FW-LS (-20 ± 5 vs. -18 ± 5%, p < 0.001), RV-4Ch-LS (-16 ± 5 vs. -14 ± 5%, p < 0.001). At multivariable analysis improvement in RV-FW-LS was associated to baseline levels of RV S' (r 0.75, p < 0.01) and RAV (r -0.32, p < 0.05). CONCLUSIONS: In a real-world scenario, 6-month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S' and right atrial volume values.

Prognosis of Coronary Atherosclerotic Burden in Non-Ischemic Dilated Cardiomyopathies.

BACKGROUND: Atherosclerosis is associated with a worse prognosis in many diseases such as ischemic cardiomyopathy, but its impact in non-ischemic dilated cardiomyopathy (dCMP) is lesser known. Our aim was to study the prognostic impact of coronary atherosclerotic burden (CAB) in patients with dCMP. METHODS: Consecutive patients with dCMP and left ventricular (LV) dysfunction diagnosed by concomitant analysis of invasive coronary angiography (ICA) and CMR imaging were identified from registry-database. CAB was measured by Gensini score. The primary composite endpoint was the occurrence of major adverse cardiovascular events (MACE) defined as cardiovascular (CV) mortality, non-fatal MI and unplanned myocardial revascularization. The results of 139 patients constituting the prospective study population (mean age 59.4 ± 14.7 years old, 74% male), average LV ejection fraction was 31.1 ± 11.02%, median Gensini score was 0 (0-3), and mid-wall late gadolinium enhancement (LGE) was the most frequent LGE pattern (42%). Over a median follow-up of 2.8 years, 9% of patients presented MACE. Patients with MACE had significantly higher CAB compared to those who were free of events (0 (0-3) vs. 3.75 (2-15), p < 0.0001). CAB remained the significant predictor of MACE on multivariate logistic analysis (OR: 1.12, CI: 1.01-1.23, p = 0.02). CONCLUSION: High CAB may be a new prognostic factor in dCMP patients.

Revascularization rates with coronary angioplasty and mortality in type 2 myocardial infarction: A meta-regression analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) represents the best therapeutic option for type-1 myocardial infarction (T1MI) in the majority of clinical settings; its role in the treatment of type-2 myocardial infarction (T2MI), however, remains unclear. We therefore sought to assess in a meta-regression analysis the impact of PCI rates on mortality in patients with T2MI according to available observational studies. METHODS: We performed a meta-regression analysis including all the studies involving in-patients affected by T2MI. We excluded studies not reporting the rate of T2MI patients undergoing PCI and not specifying absolute in-hospital or 1-year all-cause mortality. In the meta-regression analysis we used the in-hospital mortality and 1-year mortality as dependent variables and the rate of PCI as independent; regression was weighted for studies' size. RESULTS: After careful examination, 8 studies were selected for the assessment of in-hospital mortality and 8 for 1-year-mortality. We included 3155 and 3756 in-patients for in-hospital and 1-year mortality respectively. At meta-regression analysis, a borderline correlation between PCI rate and in-hospital mortality (p 0.05) and a statistically significant correlation with 1-year mortality (p < 0.01) in T2MI patients were found. CONCLUSIONS: In a meta-regression analysis higher rates of PCI on T2MI in-patients were associated with lower mortality rates both in-hospital and at 1 year. Whether this association is related to the direct effect of PCI or better general conditions of T2MI patients undergoing a PCI still remains unclear.

Chronic thromboembolic pulmonary hypertension mimicking coronary artery disease.

We report the case of 63-year-old man, complaining of dyspnea and with abnormal systolic motion of the interventricular septum at echocardiography, referred for coronary angiography and suspect coronary artery disease. In the presence of normal coronary angio, a specific work-up showed chronic thromboembolic pulmonary hypertension requiring pulmonary endarterectomy. The case highlights the need for a global cardiovascular and imaging approach in presence of poorly specific symptoms and signs of coronary artery disease.

Pulmonary Embolism and Thrombus in Transit Through Patent Foramen Ovale.

Thrombus-in-transit through a patent foramen ovale (PFO) in a patient with pulmonary embolism (PE) is a rare event with high mortality rates. We report the case a of 53-year-old woman admitted for dyspnea, cough, hemoptysis, presyncope, tachycardia, and hypotension. A recent fall down the stairs with costal trauma was also reported. At transthoracic echocardiography, dilated right atrium with the presence of a large floating thrombus was found, protruding into the left atrium through a PFO; lower extremity vascular ultrasound showed right great saphenous vein thrombosis extended over the saphenofemoral junction up to the common femoral vein. CT scan showed submassive thromboembolism; surgical thrombectomy was, therefore, performed with the closure of the PFO; an inferior vena cava filter was also positioned for the prevention of recurrent episodes of thromboembolism. The patient was discharged in therapy with apixaban 5 mg twice a day. Two-month follow up was uneventful. Large thrombi in transit through PFO can be found at transthoracic echocardiography. The management, either medical or surgical, should be aimed at preventing systemic thromboembolism.