Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

Left Ventricle Noncompaction Phenotype: Cause or Consequence?

Left ventricular noncompaction (LVNC) is commonly described as a congenital cardiomyopathy characterized by prominent myocardial trabeculae and deep intertrabecular recesses extending in the left ventricular chamber. Clinical presentation can differ considerably from asymptomatic individuals to those presenting with heart failure and other serious complications. Diagnosis is usually made by two-dimensional transthoracic echocardiography or cardiac magnetic resonance. Moreover, even if strain parameters are significantly reduced in patients with LVNC, they are not routinely investigated. Here, we report the case of a previously symptomless patient admitted to the hospital for pulmonary edema. Two-dimensional transthoracic echocardiography showed severe valvular heart disease and left ventricle pronounced trabeculation and remodeling, although speckle tracking echocardiography (STE) demonstrated only mild strain reduction. We, therefore, explore the possibility that STE may be useful to differentiate LVNC cardiomyopathy from LVNC phenotype due to severe remodeling.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.

BACKGROUND: Long-term consequences of COVID-19 are still partly known. AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up.

De Novo p.Asp3368Gly Variant of Dystrophin Gene Associated with X-Linked Dilated Cardiomyopathy and Skeletal Myopathy: Clinical Features and In Silico Analysis.

Dystrophin (DMD) gene mutations are associated with skeletal muscle diseases such as Duchenne and Becker Muscular Dystrophy (BMD) and X-linked dilated cardiomyopathy (XL-DCM). To investigate the molecular basis of DCM in a 37-year-old woman. Clinical and genetic investigations were performed. Genetic testing was performed with whole exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all available members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using an in silico prediction of pathogenicity. The index case was a 37-year-old woman diagnosed with DCM at the age of 33. A germline heterozygous A>G transversion at nucleotide 10103 in the DMD gene, leading to an aspartic acid-glycine substitution at the amino acid 3368 of the DMD protein (c.10103A>G p.Asp3368Gly), was identified and confirmed by PCR-based Sanger sequencing of the exon 70. In silico prediction suggests that this variant could have a deleterious impact on protein structure and functionality (CADD = 30). The genetic analysis was extended to the first-degree relatives of the proband (mother, father, and sister) and because of the absence of the variant in both parents, the p.Asp3368Gly substitution was considered as occurring de novo. Then, the direct sequencing analysis of her 8-year-old son identified as hemizygous for the same variant. The young patient did not present any signs or symptoms attributable to DCM, but reported asthenia and presented with bilateral calf hypertrophy at clinical examination. Laboratory testing revealed increased levels of creatinine kinase (maximum value of 19,000 IU/L). We report an early presentation of dilated cardiomyopathy in a 33-year-old woman due to a de novo pathogenic variant of the dystrophin (DMD) gene (p.Asp3368Gly). Genetic identification of this variant allowed an early diagnosis of a skeletal muscle disease in her son.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Beta-blockers and renin-angiotensin system inhibitors for Takotsubo syndrome recurrence: a network meta-analysis.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute heart failure syndrome, featured by transient left ventricular systolic dysfunction. Recurrences of TTS are not infrequent and there is no standard preventive therapy. The aim of this study was to evaluate in a network meta-analysis if beta-blockers (BB) and ACE inhibitors/angiotensin receptor blockers (ACEi/ARBs), in combination or not, can effectively prevent TTS recurrences. METHODS: We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for clinical studies published between January 2010 and September 2022. We considered all those studies including patients receiving medical therapy with BB, ACEi/ARBs. The primary outcome was TTS recurrence. RESULTS: We identified 6 clinical studies encompassing a total of 3407 patients with TTS. At 40±10 months follow-up, TTS recurrence was reported in 160 (4.7%) out of 3407 patients. Mean age was 69.8±2 years and 394 patients (11.5%) out of 3407 were male. There were no differences in terms of TTS recurrence when comparing ACEi/ARBs versus control (OR 0.83; 95% CI 0.47 to 1.47, p=0.52); BB versus control (OR 1.01; 95% CI 0.63 to 1.61, p=0.96) and ACEi/ARBs versus BB (OR 0.88; 95% CI 0.51 to 1.53, p=0.65).Combination of BB and ACEi/ARBs was also not effective in reducing the risk of recurrence versus control (OR 0.91; 95% CI 0.58 to 1.43, p=0.68) vs ACEi/ARBs (OR 0.79; 95% CI 0.46 to 1.34, p=0.38)) and vs BB (OR 0.77; 95% CI 0.49 to 1.21, p=0.26). CONCLUSIONS: Our study did not find sufficient statistical evidence regarding combination therapy with BB and ACEi/ARBs in reduction of TTS recurrence.

Flow Mediated Dilation in Systemic Sclerosis: Association with clinical findings, capillaroscopic patterns and endothelial circulating markers.

AIM: Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. METHODS: 57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. RESULTS: Compared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. CONCLUSIONS: FMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.

Acute coronary syndrome with single­lead ST segment elevation: A rare presentation of multivessel coronary artery disease.

We report the case of a 73-year-old male admitted for epigastric pain and syncope with increased troponin level and a rare electrocardiogram (a single­lead ST-elevation). Coronary angiography showed multi-vessel coronary artery disease. The patient underwent coronary angioplasty with drug-eluting stenting on left anterior descending coronary artery and drug eluting ballooning on first diagonal ostium. Coronary revascularization was completed with a staged stenting on left circumflex artery and right coronary artery. In rare cases of acute coronary syndrome, even isolated ST single lead anomalies may underlie multivessel coronary disease.

Multidisciplinary approach in cardiomyopathies: From genetics to advanced imaging.

Cardiomyopathies are myocardial diseases characterized by mechanical and electrical dysfunction of the heart muscle which could lead to heart failure and life-threatening arrhythmias. Certainly, an accurate anamnesis, a meticulous physical examination, and an ECG are cornerstones in raising the diagnostic suspicion. However, cardiovascular imaging techniques are indispensable to diagnose a specific cardiomyopathy, to stratify the risk related to the disease and even to track the response to the therapy. Echocardiography is often the first exam that the patient undergoes, because of its non-invasiveness, wide availability, and cost-effectiveness. Cardiac magnetic resonance imaging allows to integrate and implement the information obtained with the echography. Furthermore, cardiomyopathies' genetic basis has been investigated over the years and the list of genetic mutations deemed potentially pathogenic is expected to grow further. The aim of this review is to show echocardiographic, cardiac magnetic resonance imaging, and genetic features of several cardiomyopathies: dilated cardiomyopathy (DMC), hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), left ventricular noncompaction cardiomyopathy (LVNC), myocarditis, and takotsubo cardiomyopathy.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.

Meta-regression analysis on the impact of medical therapy on long-term outcome in spontaneous coronary artery dissection.

Background: Spontaneous coronary artery dissection (SCAD) is a relatively rare condition affecting predominantly young adults, with a prevalence of female sex. The best management of SCAD is still unclear and not adequately evidence-based both in the acute phase but especially over the long-term. We therefore aimed to evaluate the impact of medical therapy usually adopted for coronary artery disease on long-term outcome in SCAD patients. Methods: We performed a meta-regression analysis including all the studies evaluating the long-term outcome of patients affected by SCAD. We used long-term mortality, recurrent SCAD, admission for angina and major adverse cardio-vascular events (MACE) as dependent variables and the rates of discharge drug rates (beta-blockers, statins, renin-angiotensin-aldosterone system inhibitors, aspirin, dual antiplatelet therapy (DAPT)) as independent variables. Results: Fourteen observational studies were included with a long-term follow-up of 3.5 ± 1.7 years. No statistically significant correlations between drug therapy (beta-blockers, statins, calcium channel blockers, nitrates, renin-angiotensin-aldosterone inhibitors) and mortality, MACE, admission for angina, and SCAD recurrence were found. Higher aspirin use rates were significantly correlated with lower admission rates for angina (p < 0.05); DAPT, however, showed a borderline correlation with higher rates of SCAD recurrence (p = 0.068). Conclusions: In a meta-regression analysis including observational studies aspirin use rates correlated with lower long-term rates of admission for angina, while a borderline correlation between DAPT and rates of SCAD recurrence was found. Other drugs usually used for the treatment of coronary artery disease do not seem to impact long-term outcome of SCAD patients.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

Improvement in Left and Right Ventricular Function after Introduction of SGLT2 Inhibitors in Heart Failure Outpatients with Reduced Ejection Fraction.

BACKGROUND: Type 2 sodium-glucose cotransporter inhibitors (SGLT2i) are among the main therapeutic options for patients with chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effects of SGLT2i on the echocardiographic parameters of left (LV) and right (RV) ventricular function among outpatients with a long history of HFrEF, in optimized therapy. METHODS: We evaluated consecutive patients affected by HFrEF in whom the SGLT2i therapy was prescribed. Following a baseline evaluation (T0), in which SGLT2i was prescribed, patients were re-evaluated at 3 (T3), 6 (T6), and 12 (T12) months. RESULTS: We considered 60 patients for the analysis with a median history of HFrEF of more than seven years in optimal medical and electrical therapy. After SGLT2i therapy, LV ejection fraction and LV global longitudinal strain improved from baseline at T3, T6, and T12. Analogously, RV global and free wall longitudinal strain improved at T3 and T6. CONCLUSIONS: Our study shows that the addition of SGLT2i to the optimized therapy for HFrEF was associated with a significant improvement in both LV and RV function, thus highlighting a possible mechanism responsible for the benefit obtained with this class of drugs.

The Role of Genetics in the Management of Heart Failure Patients.

Over the last decades, the relevance of genetics in cardiovascular diseases has expanded, especially in the context of cardiomyopathies. Its relevance extends to the management of patients diagnosed with heart failure (HF), given its capacity to provide invaluable insights into the etiology of cardiomyopathies and identify individuals at a heightened risk of poor outcomes. Notably, the identification of an etiological genetic variant necessitates a comprehensive evaluation of the family lineage of the affected patients. In the future, these genetic variants hold potential as therapeutic targets with the capability to modify gene expression. In this complex setting, collaboration among cardiologists, specifically those specializing in cardiomyopathies and HF, and geneticists becomes paramount to improving individual and family health outcomes, as well as therapeutic clinical results. This review is intended to offer geneticists and cardiologists an updated perspective on the value of genetic research in HF and its implications in clinical practice.

Introduction of SGLT2 Inhibitors and Variations in Other Disease-Modifying Drugs in Heart Failure Patients: A Single-Centre Real-World Experience.

BACKGROUND: The sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a crucial therapeutic option for patients with chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single centre, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. METHODS: Consecutive patients affected by chronic heart failure (CHF) were evaluated beginning in January 2022. At the baseline clinical visit, both the patient's current medication and the prescribed treatments were recorded. Over a 6- to 12-month follow-up, changes in concomitant therapy were analysed. RESULTS: At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i: 13 with HFrEF, five with mildly reduced (HFmrEF), preserved (HFpEF) or improved (HFimpEF) ejection fraction. After the baseline assessment, SGLT2i were prescribed to 224 (64%) of the patients, including 179 (84%) with HFrEF, 27 (42%) with HFmrEF/HFimpEF, and 18 (22%) with HFpEF/HFimpEF. After follow-up, SGLT2i therapy was well tolerated and was associated with a significant increase in sacubitril/valsartan prescriptions and a decrease in diuretic use. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. CONCLUSIONS: In this single-centre, real-world study, SGLT2i were primarily prescribed to HFrEF patients who were already on other recommended drug classes for their treatment. Additionally, there was a noticeable enhancement in the prescribed therapy during a short-term follow-up. These findings further bolster the inclusion of this therapeutic approach in regular clinical practice.