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.

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.

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.

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.

ANMCO POSITION PAPER: Network Organization for the Treatment of Acute Coronary Syndrome Patients during the Emergency COVID-19 Pandemic.

The COVID-19 pandemic has become a global health emergency. In Italy, the number of people infected by SARS-COVID-2 is rapidly increasing and what emerges from the current data is that the majority do not present any symptoms or only minor flu-like symptoms. In about 20% of the patients, the disease progresses towards more complex forms (interstitial pneumonia to acute respiratory distress and multiple organ failure) with the need of hospitalization in CICU and advanced ventilator assistance. The transmission of the virus occurs very easily from the symptomatic patient s droplets from coughing and sneezing and from direct contact with persons or surfaces. In a patient presenting with ST elevation (STEMI) myocardial infarction or STEMI-like, if positive to COVID-19, the reperfusion therapeutic strategy depends on the local organization and on the possibility to access without delay a PCI COVID Center, on the basis, obviously, of the risk/benefit assessment of the individual case. However, we advise to try pursuing, in the first instance, the mechanical revascularization strategy, according to the available local possibilities.

ANMCO POSITION PAPER: The role of cardiology in the management of the health needs in the post-Covid-19 era.

At the end of 2019 a new Coronavirus appeared in China and, from there, it spread to the rest of the world. On 24th May, 2020, the confirmed cases in the world were more than 5 million and the deaths almost 350.000. At the end of May, Italy reported more than 27.000 cases among healthcare professionals and 163 deaths among physicians. The National Health Systems from almost all over the world, including Italy's, were unprepared for this pandemic, and this generated important consequences of organizational nature. All elective and urgent specialized activities were completely reorganized, and many hospital units were partially or completely converted to the care of the COVID-19 patients. A significant reduction in hospital admissions for acute heart disease were recorded during the SARS-CoV-2 pandemic and, in order to gradually resume hospital activities, the Italian National Phase 2 Plan for the partial recovery of activities, must necessarily be associated with a Phase 2 Health Plan. In regards to the cardiac outpatient activities we need to identify short term goals, i.e. reschedule the suspended outpatient activities, revise the waiting lists, review the 'timings' of the bookings. This will reduce the number of available examinations compared to the pre-Covid-19 era. The GP's collaboration could represent an important resource, a structured telephone follow-up plan is advisable with the nursing staff's involvement. It is equally important to set medium-long term goals, the pandemic could be an appropriate moment for making a virtue of necessity. It is time to reason on prescriptive appropriateness, telemedicine implementation intended as integration to the traditional management. It is time to restructure the cardiological units related to the issue of structural adjustment to the needs for functional isolation. Moreover, the creation of 'grey zones' with multidisciplinary management according to the intensity of care levels seems to be necessary as well as the identification of Covid dedicated cardiologies. Finally, the pandemic could represent the opportunity for a permanent renovation of the cardiological and territorial medicine activities.

ANMCO POSITION PAPER: The cardiological clinical activities in the transition phase of the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients' need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable ('not at risk') of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

ANMCO POSITION PAPER: Considerations on in-hospital cardiological consultations and cardiology outpatient clinics during the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 have become in a short time a worldwide health emergency. Due to cardiovascular implications of COVID-19 and to very frequent previous cardiovascular disorders of COVID-19 patients, it is presently crucial that Cardiologists are fully aware of COVID-19 related epidemiological, pathophysiological and therapeutic problems, in order to manage at best the present emergency by appropriate protocols developed on the basis of the competences acquired and shared on the field. The aim of this document is to propose algorithms for the management of cardiovascular diseases during COVID-19 emergency with the objective of providing patients with optimal care, minimizing contagion risk and appropriately managing personal protective equipment.

ANMCO POSITION PAPER: The management of suspect or confirmed COVID-19 patients needing urgent electrophysiology and/or electrostimulation procedures.

The aim of this document is the management and organization of patients in need of urgent access to electrophysiology (EP) and pacing procedures during the COVID-19 emergency. Specifically, non-deferrable procedures or irreplaceable with a drug therapy prior to the resolution of the COVID-19 virus emergency [pacemaker (PM) implant/replacement/urgent defibrillator (implantable cardioverter-defibrillator, ICD) or arrhythmic storm or other indication of non-deferrable ablation]. The pacing and electrophysiological procedures urgent as they may be, less and less frequently represent situations of emergency, therefore for almost all cases, it is possible to perform a swab test to determine the positivity to COVID-19 of the patient. In cases where this is not possible, due to situations of emergency, the recommendations and procedures we have indicated are advisable, if not mandatory, in order to avoid the spreading of the virus to healthcare personnel and other patients.

[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.

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.

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.

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.

Ventilation strategies in cardiogenic shock: Insights from the AltShock-2 registry.

AIMS: To describe the use and the relation to outcome of different ventilation strategies in a contemporary, large, prospective registry of cardiogenic shock patients. METHODS AND RESULTS: Among 657 patients enrolled from March 2020 to November 2023, 198 (30.1%) received oxygen therapy (OT), 96 (14.6%) underwent non-invasive ventilation (NIV), and 363 (55.3%) underwent invasive mechanical ventilation (iMV). Patients in the iMV group were significantly younger compared to those in the NIV and OT groups (63 vs. 69 years, p < 0.001). There were no significant differences between groups regarding cardiovascular risk factors. Patients with SCAI B and C were more frequently treated with OT and NIV compared to iMV (65.1% and 65.4% vs. 42.6%, respectively, p > 0.001), while the opposite trend was observed in SCAI D patients (12% and 12.2% vs. 30.9%, respectively, p < 0.001). All-cause mortality at 24 h did not differ amongst the three groups. The 60-day mortality rates were 40.2% for the iMV group, 26% for the OT group, and 29.3% for the NIV group (p = 0.005), even after excluding patients with cardiac arrest at presentation. In the multivariate analysis including SCAI stages, NIV was not associated with worse mortality compared to iMV (hazard ratio 1.97, 95% confidence interval 0.85-4.56), even in more severe SCAI stages such as D. CONCLUSIONS: Compared to previous studies, we observed a rising trend in the utilization of NIV among cardiogenic shock patients, irrespective of aetiology and SCAI stages. In this clinical scenario, NIV emerges as a safe option for appropriately selected patients.

[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.