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).

Impella versus VA-ECMO for the treatment of patients with cardiogenic shock: the Impella Network Project - observational study protocol for cost-effectiveness and budget impact analyses.

INTRODUCTION: The treatment of patients with cardiogenic shock (CS) encompasses several health technologies including Impella pumps and venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, while they are widely used in clinical practice, information on resource use and quality of life (QoL) associated with these devices is scarce. The aim of this study is, therefore, to collect and comparatively assess clinical and socioeconomic data of Impella versus VA-ECMO for the treatment of patients with severe CS, to ultimately conduct both a cost-effectiveness (CEA) and budget impact (BIA) analyses. METHODS AND ANALYSIS: This is a prospective plus retrospective, multicentre study conducted under the scientific coordination of the Center for Research on Health and Social Care Management of SDA Bocconi School of Management and clinical coordination of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute in Milan. The Impella Network stemmed for the purposes of this study and comprises 17 Italian clinical centres from Northern to Southern Regions in Italy. The Italian network qualifies as a subgroup of the international Impella Cardiac Surgery Registry. Patients with CS treated with Impella pumps (CP, 5.0 or 5.5) will be prospectively recruited, and information on clinical outcomes, resource use and QoL collected. Economic data will be retrospectively matched with data from comparable patients treated with VA-ECMO. Both CEA and BIA will be conducted adopting the societal perspective in Italy. This study will contribute to generate new socioeconomic evidence to inform future coverage decisions. ETHICS AND DISSEMINATION: As of May 2024, most of the clinical centres submitted the documentation to their ethical committee (N=13; 76%), six centres received ethical approval and two centres started to enrol patients. Study results will be published in peer-reviewed publications and disseminated through conference presentations.

Myocardial Work Indices Predict Hospitalization in Patients with Advanced Heart Failure.

BACKGROUND: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW's feasibility in the prognostic stratification of AdHF. METHODS: We retrospectively screened patients with AdHF who accessed our hospital in 2018-2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). RESULTS: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50-62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323-868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan-Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. CONCLUSIONS: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

[Blood gas analysis in the intensive cardiac care unit]. / La rapida lettura dell'emogasanalisi in unità di terapia intensiva cardiologica.

Arterial blood gas (ABG) analysis is a simple and quick test that can provide multiple respiratory and metabolic parameters. The interpretation of ABG analysis and acid-base disorders represents one of the most complex chapters of clinical medicine. In this brief review, the authors propose a rational approach that sequentially analyzes the information offered by the ABG to allow a rapid classification of the respiratory, metabolic or mixed disorder. The patient's history and clinical-instrumental assessment are the framework in which to insert the information derived from the ABG analysis in order to characterize the critical heart patient.

Prognostic Value of APACHE IV Score in Patients Bridged to Heart Transplantation on ECMO.

BACKGROUND: Methods for risk stratification of candidates for heart transplantation (HTx) supported by extracorporeal membrane oxygenation (ECMO) are limited. We evaluated the reliability of the APACHE IV score to identify the risk of mortality in this patient subset in a multicenter study. METHODS: Between January 2010 and December 2022, 167 consecutive ECMO patients were bridged to HTx; they were divided into two groups, according to a cutoff value of APACHE IV score, obtained by receiver operating characteristic curve analysis for 90-day mortality. Kaplan-Meier survival curves were plotted, and compared through the log-Rank test. Cox regression model was used to estimate which factors were associated with survival. RESULTS: The 90-day mortality prediction of the APACHE IV score showed an area under the curve of 0.87 (95% CI: 0.80-0.94), with a cutoff value of 49 (specificity 91.7%-sensibility 69.6%). 125 patients (74.8%) showed an APACHE IV score value < 49 (Group A), and 42 (25.2%) ≥ 49 (Group B). 90-day mortality was 11.2% in Group A and 76.2% in Group B (p < 0.01). Survival at 1 and 5 years was 85.5%, 77% versus 23.4%, 23.4% (p < 0.01) in Groups A and B. Mortality correlated at univariable analysis with recipient age, body mass index, mechanical ventilation, APACHE IV score, and platelets number. At multivariable analysis only APACHE IV score (HR: 1.07 [1.05-1.09, 95% CI]) independently affected survival. CONCLUSIONS: The APACHE IV score represents a powerful predictor of survival in patients bridged to HTx on ECMO support, and could guide candidacy of patients on ECMO.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). AIM: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. METHODS: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. RESULTS: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. CONCLUSION: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Right ventricular dysfunction in left ventricular assist device candidates: is it time to change our prospective?

The use of left ventricular assist devices (LVAD) has significantly increased in the last years, trying to offer a therapeutic alternative to heart transplantation, in light also to the significant heart donor shortage compared to the growing advanced heart failure population. Despite technological improvements in the devices, LVAD-related mortality is still fairly high, with right heart failure being one of the predominant predictors. Therefore, many efforts have been made toward a thorough right ventricular (RV) evaluation prior to LVAD implant, considering clinical, laboratory, echocardiographic, and invasive hemodynamic parameters. However, there is high heterogeneity regarding both which predictor is the strongest as well as the relative cut-off values, and a consensus has not been reached yet, increasing the risk of facing patients in which the distinction between good or poor RV function cannot be surely reached. In parallel, due to technological development and availability of mechanical circulatory support of the RV, LVADs are being considered even in patients with suboptimal RV function. The aim of our review is to analyze the current evidence regarding the role of RV function prior to LVAD and its evaluation, pointing out the extreme variability in parameters that are currently assessed and future prospective regarding new diagnostic tools. Finally, we attempt to gather the available information on the therapeutic strategies to use in the peri-operative phase, in order to reduce the incidence of RV failure, especially in patients in which the preoperative evaluation highlighted some conflicting results with regard to ventricular function.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

Differences between cardiogenic shock related to acute decompensated heart failure and acute myocardial infarction.

AIMS: The present analysis from the multicentre prospective Altshock-2 registry aims to better define clinical features, in-hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF-CS) as compared with that complicating acute myocardial infarction (AMI-CS). METHODS AND RESULTS: All patients with AMI-CS or ADHF-CS enrolled in the Altshock-2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF-CS patients as compared with AMI-CS. In-hospital length of stay and mortality were secondary endpoints. One-hundred-ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI-CS (80% ST-elevated myocardial infarction and 20% non-ST-elevated myocardial infarction) and 89 ADHF-CS. As compared with AMI-CS, ADHF-CS patients were younger [63 (IQR 59-76) vs. 67 (IQR 54-73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0-2.6) vs. 1.2 (IQR 1.0-1.4) mg/dL, P < 0.001], bilirubin [1.3 (IQR 0.9-2.3) vs. 0.6 (IQR 0.4-1.1) mg/dL, P = 0.01], and central venous pressure values [14 mmHg (IQR 8-12) vs. 10 mmHg (IQR 7-14),P = 0.01]. Norepinephrine was the most common catecholamine used in AMI-CS (79.3%), whereas epinephrine was used more commonly in ADHF-CS (65.5%); 75.8% vs. 46.6% received a temporary mechanical support in AMI-CS and ADHF-CS, respectively (P < 0.001). Length of hospital stay was longer in the latter [28 (IQR 13-48) vs. 17 (IQR 9-29) days, P = 0.001]. Heart replacement therapies were more frequently used in the ADHF-CS group (heart transplantation 13.5% vs. 0% and left ventricular assist device 11% vs. 2%, P < 0.01 and 0.01, respectively). In-hospital mortality was 41.1% (38.6% AMI-CS vs. 43.8% ADHF-CS, P = 0.5). CONCLUSIONS: ADHF-CS is characterized by a higher prevalence of end-organ and biventricular dysfunction at presentation, a longer hospital length of stay, and higher need of heart replacement therapies when compared with AMI-CS. In-hospital mortality was similar between the two aetiologies. Our data warrant development of new management protocols focused on CS aetiology.

[Practical approach to the patient with fever in the intensive cardiac care unit: diagnostic framework and therapy notes]. / Approccio pratico al paziente con febbre in terapia intensiva cardiologica: inquadramento diagnostico e cenni di terapia.

The management of the patient with fever in the intensive cardiac care unit begins with a thorough evaluation of the patient, particularly symptoms, clinical history and physical examination, to provide information regarding the origin of the fever. The global evaluation of the patient should be integrated with blood and microbiological tests, in particular blood culture and swab. The laboratory, microbiologic or radiologic tests could be more or less detailed and targeted depending on the type of suspected infection and clinical conditions of the patient. When therapy is necessary, it is crucial to switch, as soon as possible, from broad spectrum antibiotic therapy to antibiotic therapy based on the results of the microbiological exams. Antibiotic therapy could be associated with antipyretic and specific organ support therapy when necessary.

[Electrical storm management in the cardiac care unit]. / Gestione della tempesta aritmica in terapia intensiva cardiologica.

Electrical storm (ES) is characterized by at least three separate episodes of ventricular arrhythmia (VA) over 24 h that require treatment or an incessant VA lasting >12 h. The incidence is higher in patients with implantable cardioverter-defibrillators (ICDs) in secondary prevention and the main manifestation is monomorphic VA. ES onset represents a major event in the history of patients with cardiomyopathies that significantly worsens prognosis. The management of ES is complex and requires a multidisciplinary approach including a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, ablation, and neuromodulation procedures. ES early recognition and prompt treatment initiation increase the chances of therapeutic success. Each one of these aspects will be properly discussed in the present decalogue. Notably, ES management remains a challenge, with only limited available evidence from small retrospective series and a substantial lack/limited number of randomized or prospective trials. The spectrum of available antiarrhythmic drugs is limited, as well as their efficacy. The future hope is that larger prospective studies will be able to answer important questions, concerning the most effective pharmacologic strategies, the timing for the invasive treatment, the indications for acute neuromodulation strategies and for the circulatory support tools.

Right ventricular myocardial work for the prediction of early right heart failure and long-term mortality after left ventricular assist device implant.

AIMS: Right heart failure (RHF) after left ventricular assist device (LVAD) implant is burdened by high morbidity and mortality rates and should be prevented by appropriate patient selection. Adequate right ventricular function is of paramount importance but its assessment is complex and cannot disregard afterload. Myocardial work (MW) is a non-invasive Speckle Tracking Echocardiography-derived method to estimate pressure-volume loops. The aim of this study was to evaluate the performance of right ventricular myocardial work to predict RHF and long-term mortality after LVAD implant. METHODS AND RESULTS: Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam prior to LVAD implant were excluded. MW analysis was performed. The primary endpoints were early RHF (<30 days from LVAD implant) and death at latest available follow-up. We included 23 patients (mean age 64 ± 8 years, 91% men). Median follow-up was 339 days (IQR: 30-1143). Early RHF occurred in six patients (26%). A lower right ventricular global work efficiency [RVGWE, OR 0.86, 95% confidence intervals (CI) 0.76-0.97, P = 0.014] was associated with the occurrence of early RHF. Among MW indices, the performance for early RHF prediction was greatest for RVGWE [area under the curve (AUC) 0.92] and a cut-off of 77% had a 100% sensitivity and 82% specificity. At long-term follow-up, death occurred in 4 of 14 patients (28.6%) in the RVGWE > 77% group and in 6 of 9 patients (66.7%) in the RVGWE < 77% group (HR 0.25, 95% CI 0.07-0.90, P = 0.033). CONCLUSION: RVGWE was a predictor of early RHF after LVAD implant and brought prognostic value in terms of long-term mortality.

Tricuspid Regurgitation Velocity and Mean Pressure Gradient for the Prediction of Pulmonary Hypertension According to the New Hemodynamic Definition.

BACKGROUND: The hemodynamic definition of PH has recently been revised with unchanged threshold of peak tricuspid regurgitation velocity (TRV). The aim of this study was to evaluate the predictive accuracy of peak TRV for PH based on the new (>20 mmHg) and the old (>25 mmHg) cut-off value for mean pulmonary artery pressure (mPAP) and to compare it with the mean right ventricular-right atrial (RV-RA) pressure gradient. METHODS: Patients with advanced heart failure were screened from 2016 to 2021. The exclusion criteria were absent right heart catheterization (RHC) results, chronic obstructive pulmonary disease, any septal defect, inadequate acoustic window or undetectable TR. The mean RV-RA gradient was calculated from the velocity-time integral of TR. RESULTS: The study included 41 patients; 34 (82.9%) had mPAP > 20 mmHg and 24 (58.5%) had mPAP > 25 mmHg. The AUC for the prediction of PH with mPAP > 20 mmHg was 0.855 for peak TRV and mean RV-RA gradient was 0.811. AUC for the prediction of PH defined as mPAP > 25 mmHg for peak TRV was 0.860 and for mean RV-RA gradient was 0.830. A cutoff value of 2.4 m/s for peak TRV had 65% sensitivity and 100% positive predictive value for predicting PH according to the new definition. CONCLUSIONS: Peak TRV performed better than mean RV-RA pressure gradient in predicting PH irrespective of hemodynamic definitions. Peak TRV performed similarly with the two definitions of PH, but a lower cutoff value had higher sensitivity and equal positive predictive value for PH.

Aortic root/left ventricular diameters golden ratio in competitive athletes.

BACKGROUND: The athlete's heart is a well-known phenomenon characterized by a harmonic remodelling that affects the cardiac chambers. However, whether mild-to-moderate aortic dilatation can be considered normal in athletes is debated. This study aimed to evaluate the ratio between left ventricular (LV) size and aortic dimensions, reporting the normal values of the ratio between the aortic root diameters at the level of the sinuses of Valsalva and LV diameters (AoD/LVEDD ratio) in a wide cohort of competitive athletes. MATERIALS AND METHODS: Competitive athletes were compared with sedentary subjects and patients with aortic dilatation. 1901 subjects who underwent echocardiography from 2019 to 2022 were retrospectively enrolled: 993 athletes (74% males, mean age 26 ± 7 years), 410 sedentary (74.1% males, mean age 29 ± 11 years) and 498 patients with aortic dilatation (74.3% males, mean age 56 ± 7 years). RESULTS: Patients with aortic dilatation had both an absolute (39.2 ± 2.4 mm) and indexed (19.4 ± 2.2 mm/m2) aortic diameter larger than athletes (30.6 ± 3.2 mm; 16.1 ± 1.5 mm/m2, p < 0.05) and sedentary subjects (30.5 ± 3.1 mm; 16.5 ± 1.6 mm/m2, p < 0.05), with no differences between athletes and sedentary subjects. The AoD/LVEDD ratio was lower in athletes (0.59 ± 0.06) compared to controls (0.65 ± 0.05, p < 0.05) and patients with aortic dilatation (0.81 ± 0.06, p < 0.05). The patients with aortopathy had the lowest LVEDD/AoD ratio, while competitive athletes had the highest, with values of 1.71 ± 0.16 in the latter (overall p value<0.001). CONCLUSIONS: In this study, we reported the AoD/LVEDD and LVEDD/AoD ratio values in a cohort of healthy athletes, additional parameters that could help confirm the harmonic remodelling in the athlete's heart.

Heart transplantation and anti-HLA antibodY: myocardial dysfunction and prognosis - HeartLAy study.

AIMS: The presence of anti-human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non-invasive parameters early signs of myocardial dysfunction in the presence of anti-HLA antibodies but without evidence of antibody-mediated rejection (AMR) and its possible prognostic impact. METHODS AND RESULTS: A total of 113 heart-transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA-' (63 patients)], based on the presence of anti-HLA antibodies. Each patient was followed for 2 years after the enrolment, recording episodes of AMR, ACR, CAV, and mortality. Clinical characteristics were similar between the two groups. Among laboratory data, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin values were significantly higher in the presence of anti-HLA antibodies (P < 0.001 and P = 0.003, respectively). The echocardiographic parameters that showed a statistically significant difference between the two groups were deceleration time of E wave (DecT E, P < 0.001), left ventricular global longitudinal strain (P < 0.001), tricuspid annular plane systolic excursion (P = 0.011), tricuspid S' wave (P = 0.002), and free wall right ventricular longitudinal strain (fwRVLS, P = 0.027), whereas left atrial strain did not differ significantly (P = 0.408). Univariate analysis showed that anti-HLA antibodies were associated with the development of CAV at both 1 and 2 year follow-up [odds ratio (OR) 11.90, 95% confidence interval (CI) 1.43-90.79, P = 0.022 and OR 3.37, 95% CI 1.78-9.67, P = 0.024, respectively]. Bivariate analysis demonstrated that both fwRVLS and DecT E were predictors of CAV development independently from HLA status. CONCLUSIONS: The presence of circulating anti-HLA antibodies is correlated with a mild cardiac dysfunction, even in the absence of AMR, and CAV development. Interestingly, reduced values of DecT E and fwRVLS were predictors of future development of CAV, independently from anti-HLA antibody.

[The hypoxic patient in the intensive cardiac care unit: from nasal cannulas to oro-tracheal intubation]. / Il paziente ipossico in unità di terapia intensiva cardiologica: dalle cannule nasali all'intubazione oro-tracheale.

Acute respiratory failure is a frequent complication of patients admitted to the intensive cardiac care unit and it is associated with a poor short- and long-term outcome. Acute respiratory failure can be managed with traditional oxygen therapy, with high-flow nasal cannula, continuous positive airway pressure, non-invasive ventilation or invasive ventilation according to clinical and blood gas condition. The use of advanced respiratory therapies is associated with both respiratory and hemodynamic effects, therefore the intensivist cardiologist should know deeply these respiratory devices. The intensivist cardiologist should perform an early diagnosis of acute respiratory failure, an appropriate selection of the respiratory device, and accurate monitoring and management to obtain clinical improvement and to avoid mechanical invasive ventilation.

[ANMCO Position paper: Inclisiran: an innovative therapeutic approach for the clinical management of hypercholesterolemia]. / Position paper ANMCO: Inclisiran: un approccio terapeutico innovativo per la gestione dell'ipercolesterolemia.

Research focused on lipid-lowering treatments has led to the development of new therapeutic options aimed at cardiovascular risk reduction. Gene silencing represents one of the most innovative approaches to reduce low-density lipoprotein cholesterol (LDL-C). Inclisiran is a small interfering RNA that inhibits proprotein convertase subtilisin/kexin type 9 synthesis and promotes LDL-C clearance by enhancing LDL-C receptor expression on hepatocyte cell surface. Several clinical studies have demonstrated inclisiran efficacy in terms of LDL-C reduction (~50%) with a dosage regimen of 300 mg administered twice a year after the first two doses administered at time 0 and after 90 days. Inclisiran use has recently been approved by the European and American drug regulatory agencies as a therapeutic option in addition to the maximum tolerated statin therapy in adults with primary hypercholesterolemia or mixed dyslipidemia who need further LDL-C reduction.

Pressure-strain loops unveil haemodynamics behind mechanical circulatory support systems.

AIMS: Mechanical circulatory support (MCS) systems are increasingly employed in cardiogenic shock and advanced heart failure. A thorough understanding of the complex interactions occurring among heart, vasculature, and device is essential to optimize patient's management. The aim of this study is to explore non-invasive haemodynamic profiling of patients undergoing MCS based on pressure-strain (PS) analysis. METHODS: Clinical and echocardiographic data from consecutive patients undergoing different MCS systems positioning/implantation admitted to the third level cardiological intensive care unit of Siena Hospital from August 2021 to November 2021 were retrospectively reviewed. Patients without a useful echocardiographic exam or without arterial blood pressure recording at the time of echocardiography were excluded. Myocardial work analysis was performed in the included patients. RESULTS: We reviewed 18 patients, of which nine were excluded. Included patients were three patients with intra-aortic balloon pump (IABP), two patients with durable left ventricular assist device (dLVAD), two patients with Impella®, one patient with extracorporeal membrane oxygenation (ECMO), and one patient with ECMO and IABP. Myocardial work analysis was feasible in each included patient. The use of IABP shifted the PS curve rightward and downward. Global work index (GWI) and global wasted work (GWW) decreased after IABP positioning, whereas global work efficiency (GWE) increased. The use of continuous-flow pumps, whether temporaneous (Impella®) or long term (dLVAD), induced a change in the PS loop morphology, with a shift towards a triangular shape. ECMO positioning alone resulted in a narrowing of the PS loop, with a decrease in GWI and GWE and an increase in GWW and mean arterial pressure. The combined used of IABP with ECMO widened the PS loop and improved GWI and GWE. CONCLUSIONS: PS loops analysis in patients undergoing MCS seems to be feasible and may unveil MCS-induced haemodynamic variations. Myocardial work could be used to monitor ventricular-arterial-device coupling and guide tailored MCS management.