The new 2023 ESC guidelines for the management of cardiomyopathies: a guiding path for cardiologist decisions.

In the ESC 2023 guidelines, cardiomyopathies are conservatively defined as 'myocardial disorders in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to cause the observed myocardial abnormality'. They are morpho-functionally classified as hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy with the addition of the left ventricular non-dilated cardiomyopathy that describes intermediate phenotypes not fulfilling standard disease definitions despite the presence of myocardial disease on cardiac imaging or tissue analysis. The new ESC guidelines provide 'a guide to the diagnostic approach to cardiomyopathies, highlight general evaluation and management issues, and signpost the reader to the relevant evidence base for the recommendations'. The recommendations and suggestions included in the document provide the tools to build up pathways tailored to specific cardiomyopathy (phenotype and cause) and define therapeutic indications, including target therapies where possible. The impact is on clinical cardiology, where disease-specific care paths can be assisted by the guidelines, and on genetics, both clinics and testing, where deep phenotyping and participated multi-disciplinary evaluation provide a unique tool for validating the pathogenicity of variants. The role of endomyocardial biopsy remains underexploited and confined to particular forms of restrictive cardiomyopathy, myocarditis, and amyloidosis. New research and development will be needed to cover the gaps between science and clinics. Finally, the opening up to disciplines such as bioinformatics, bioengineering, mathematics, and physics will support clinical cardiologists in the best governance of the novel artificial intelligence-assisted resources.

Ethylene glycol poisoning requiring veno-arterial ECMO: A case report.

Supportive care is the cornerstone of the poisoned patient's treatment, waiting for eventual antidotes to act. We recently treated a case of a severe Ethylene Glycol intoxication with early-onset veno-arterial ECMO. The patient was taken to our Emergency Department with the suspicion of acute cerebrovascular accident, since he was found unconscious at home. The arterial blood gas and blood tests showed a severe metabolic acidosis with high serum lactates and creatinine levels. The cerebral Computed Tomography was negative. The rapid increase in serum lactates suggested Ethylene Glycol intoxication. Although the patient was not in shock yet, arterial and venous introducers were placed in to the femoral vessels so that when the patient showed the first signs of cardiogenic shock, veno-arterial ECMO could be initiated in a very short time. The hemodynamic state progressively improved and V-A ECMO was removed after 16 h of support with complete recovery.

A brief clinical case of monitoring of oxygenator performance and patient-machine interdependency during prolonged veno-venous extracorporeal membrane oxygenation.

Monitoring veno-venous extracorporeal membrane oxygenation (vvECMO) during 76 days of continuous support in a 42-years old patient with end-stage pulmonary disease, listed for double-lung transplantation. Applying a new monitor (Landing®, Eurosets, Medolla, Italy) and describing how measured and calculated parameters can be used to understand the variable interdependency between artificial membrane lung (ML) and patient native lung (NL). During vvECMO, in order to understand how the respiratory function is shared between ML and NL, ideally we should obtain data about oxygen transfer and CO2 removal, both by ML and NL. Measurements for NL can be made on the mechanical ventilator. Measurements for ML are typically made from gas analysis on blood samples drawn from the ECMO system before and after the oxygenator, and therefore are non-continuous. Differently, the Landing monitor provides a continuous measurement of the oxygen transfer from the ML, combined with hemoglobin level, saturation of drained blood and saturation of reinfused blood. Moreover, the Landing monitor provides hemodynamics data about circulation through the ECMO system, with blood flow, pre-oxygenator pressure and post-oxygenator pressure. Of note, measurements include the drain negative pressure, whose monitoring may be particularly useful to prevent hemolysis. Real-time monitoring of vvECMO provides data helpful to understand the complex picture of a patient with severely damaged lungs on one side and an artificial lung on the other side. Data from vvECMO monitoring may help to adapt the settings of both mechanical ventilator and vvECMO. Data about oxygen transfer by the oxygenator are important to evaluate the performance of the device and may help to avoid unnecessary replacements, thus reducing risks and costs.

Long-term survival following surgery for endomyocardial fibrosis.

We report a successful follow-up after 28 years of a woman with obliterative restrictive endomyocardial fibrosis (EMF) that underwent complete surgical decortication with simultaneous mitral and tricuspid bioprosthetic valve replacement in 1982 and underwent successful reoperation for the structural failure of biological prostheses after 25 years.

First- Versus New-Generation Drug-Eluting Stents in Patients With Heart Transplant With Cardiac Allograft Vasculopathy.

Although several studies have previously reported on the efficacy of percutaneous coronary intervention (PCI) with first-generation drug-eluting stents (DES) in heart transplant patients with cardiac allograft vasculopathy, few data regarding new-generation DES are currently available. We sought to compare the efficacy of new-generation versus first-generation DES in 90 consecutive patients with heart transplant (113 de novo coronary lesions) who underwent urgent or elective PCI with first-generation (28 patients) or new-generation (62 patients) DES. For each patient, the severity of cardiac allograft vasculopathy and postprocedural extent of revascularization were quantified calculating baseline and residual SYNTAX score, respectively. The primary end point was a composite of major adverse cardiac events-myocardial infarction, cardiovascular death, or target vessel revascularization-at 3 years. Overall, the median baseline SYNTAX score was 8 (5 to 15), and a total number of stents per patient of 1.6 ± 0.9 was implanted. Post-PCI residual SYNTAX score was 1.5 (0 to 4), with 13 patients having a score >8. At 3 years, the Kaplan-Meier estimate of freedom from major adverse cardiac events was 64%, with no differences between first-generation and new-generation DES groups (log-rank test p = 0.269). Nevertheless, patients treated with new-generation DES experienced a lower rate of target vessel revascularization (15% vs 31%, log-rank test p = 0.058). In the multivariate Cox regression analysis, a post-PCI residual SYNTAX score >8 (hazard ratio 2.37, confidence interval 0.98 to 5.73, p = 0.054) was identified as an independent predictor of the primary end point.

Left atrium veno-arterial extra corporeal membrane oxygenation as temporary mechanical support for cardiogenic shock: A case report.

BACKGROUND: Veno-arterial extra corporeal membrane oxygenation (VA-ECMO) support is commonly complicated with left ventricle (LV) distension in patients with cardiogenic shock. We resolved this problem by transeptally converting VA-ECMO to left atrium veno-arterial (LAVA)-ECMO that functioned as a temporary paracorporeal left ventricular assist device to resolve LV distension. In our case LAVA-ECMO was also functioning as a bridge-to-transplant device, a technique that has been scarcely reported in the literature. CASE SUMMARY: A 65 year-old man suffered from acute myocardial injury that required percutaneous stents. Less than two weeks later, noncompliance to antiplatelet therapy led to stent thrombosis, cardiogenic shock, and cardiac arrest. Femoro-femoral VA-ECMO support was started, and the patient underwent a second coronary angiography with re-stenting and intra-aortic balloon pump placement. The VA-ECMO support was complicated by left ventricular distension which we resolved via LAVA-ECMO. Unfortunately, episodes of bleeding and sepsis complicated the clinical picture and the patient passed away 27 d after initiating VA-ECMO. CONCLUSION: This clinical case demonstrates that LAVA-ECMO is a viable strategy to unload the LV without another invasive percutaneous or surgical procedure. We also demonstrate that LAVA-ECMO can also be weaned to a left ventricular assist device system. A benefit of this technique is that the procedure is potentially reversible, should the patient require VA-ECMO support again. A transeptal LV venting approach like LAVA-ECMO may be indicated over ImpellaTM in cases where less LV unloading is required and where a restrictive myocardium could cause LV suctioning. Left ventricular over-distention is a well-known complication of peripheral VA-ECMO in cardiogenic shock and LAVA ECMO through transeptal cannulation offers a novel and safe approach for treating LV overloading, without the need of an additional percutaneous access.

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: Relationship between treated branches and outcome.

BACKGROUND: In patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) it is important to minimize residual obstructions, in order to achieve low postoperative pulmonary vascular resistances and better clinical results. The aim of the study was to test the hypothesis that the greater the number of pulmonary artery branches treated at surgery, the better the hemodynamic and clinical outcome after PEA. METHODS: In 564 consecutive CTEPH patients undergoing PEA the count of the number of treated branches was performed directly on the surgical specimens. Post-operative follow-up visits were scheduled at 3 months and 12 months after surgery including right heart catheterization and modified Bruce test. RESULTS: The population was divided into tertiles based on the number of treated branches: Group 1 (from 4 to 30 treated branches, n = 194 patients); Group 2 (from 31 to 43 treated branches, n = 190 patients); Group 3 (from 44 to 100 treated branches, n = 180 patients). At 3 and at 12 months after PEA, after adjustment for confounders, patients in the highest tertile of treated branches had significantly lower values of pulmonary vascular resistance and higher values of pulmonary arterial compliance as compared to the other two groups (p < 0.002). Hospital mortality was 3% in Group 3, 6% in Group 2 and 10% in Group 1 (overall p = 0.035). CONCLUSIONS: In CTEPH patients undergoing PEA, a higher number of treated pulmonary artery branches is associated with a better hemodynamic and a better clinical outcome at 3 months and 12 months after surgery.

Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.

BACKGROUND: An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. OBJECTIVES: The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. MATERIALS: The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. RESULTS: ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. CONCLUSIONS: The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.

Heart rate control and haemodynamic improvement with ivabradine in cardiogenic shock patient on mechanical circulatory support.

AIMS: Cardiogenic shock (CS) is a life-threatening condition due to primary cardiac dysfunction. First-line therapy involves drug administration (including inotropes and/or vasopressors) up to mechanical circulatory support. Tachycardia is a frequent compensatory mechanism in response to hypotension and low cardiac output or a side effect related to inotropic drugs. Ivabradine selectively acts on the IKf channel in the sinoatrial node to reduce sinus heart rate without affecting inotropism. Its use, in small non-randomized series of patients with CS without mechanical circulatory support, was safe and well tolerated. METHODS AND RESULTS: We present the use of ivabradine in six patients with CS undertaking veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and a matched cohort of selected patients with similar features who did not receive ivabradine. Data regarding haemodynamic and echocardiographic monitoring, oxygenation, renal function, mechanical circulatory support, inotropes, and vasopressors doses were collected before (t0), at 12 (t1), 24 (t2), and 48 (t3) h after ivabradine administration. Ivabradine administration led to a significant heart rate reduction of 20.83 [95% confidence interval (CI) -27.2 to -14.4] b.p.m. (<0.01). Echo-derived left ventricular native stroke volume (SV) significantly increased by +7.83 (95% CI 4.74-10.93) mL (P < 0.001) with a parallel reduction of VA-ECMO support [-170 (95% CI -225.05 to -114.95)]. Noradrenaline was down-titrated over the observation period in all patients (P = 0.016). CONCLUSION: A significant reduction in heart rate was observed after ivabradine administration. This was associated with a native ventricular SV improvement allowing the reduction of extracorporeal flow support and vasopressors administration.

Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy in Heart Transplantation: New Strategies and Preliminary Results in Endomyocardial Biopsies.

Tacrolimus (TAC) is an immunosuppressant drug approved both in the US and in the EU, widely used for the prophylaxis of organ rejection after transplantation. This is a critical dose drug: low levels in whole blood can lead to low exposure and a high risk of acute rejection, whereas overexposure puts patients at risk for toxicity and infection. Both situations can occur at whole-blood concentrations considered to be within the narrow TAC therapeutic range. We assumed a poor correlation between TAC trough concentrations in whole blood and the incidence of acute rejection; therefore, we propose to study TAC concentrations in endomyocardial biopsies (EMBs). We analyzed 70 EMBs from 18 transplant recipients at five scheduled follow-up visits during the first year post-transplant when closer TAC monitoring is mandatory. We observed five episodes of acute rejection (grade 2R) in three patients (2 episodes at 0.5 months, 2 at 3 months, and 1 at 12 months), when TAC concentrations in EMBs were low (63; 62; 59; 31; 44 pg/mg, respectively), whereas concentrations in whole blood were correct. Our results are preliminary and further studies are needed to confirm the importance of this new strategy to prevent acute rejection episodes.

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy.

BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.

[Early diagnosis and management of cardiac allograft vasculopathy: is it time for a standardized approach?] / Individuazione precoce e gestione della coronaropatia nel cuore trapiantato: è tempo per una uniformità di approccio?

Cardiac allograft vasculopathy (CAV) still represents the main cause of long-term graft loss after heart transplantation. Its silent clinical presentation makes an early identification difficult, with relevant implications for a standardized follow-up. Although technological advances have provided sophisticated non-invasive techniques for CAV assessment, intravascular ultrasound in conjunction with coronary angiography is still the gold standard to detect rapidly progressive CAV and to provide prognostic information during follow-up. Current guidelines recommend annual coronary angiography during the first 5 years and every 2 years thereafter. Although commonly performed, coronary angiography has multiple limitations, especially in young patients and in case of chronic kidney disease. This article aims to review the literature about the monitoring of CAV and to propose an ideal and individualized pathway for early diagnosis of CAV in transplanted patients, based on their cardiovascular risk.

Immune Response to BNT162b2 in Solid Organ Transplant Recipients: Negative Impact of Mycophenolate and High Responsiveness of SARS-CoV-2 Recovered Subjects against Delta Variant.

The immunogenicity of severe acute respiratory syndrome 2 virus (SARS-CoV-2) vaccines in immunocompromised patients remains to be further explored. Here, we evaluated the immunogenicity elicited by complete vaccination with BNT162b2 vaccine in solid organ transplant recipients (SOTRs). A cohort of 110 SOTRs from Northern Italy were vaccinated with two doses of BNT162b2 mRNA vaccine and prospectively monitored at baseline and after 42 days. Both SARS-CoV-2 naïve and recovered subjects were included. Humoral response elicited by vaccination, including SARS-CoV-2 neutralizing antibodies (SARS-CoV-2 NT Abs), was evaluated; additionally, ex-vivo ELISpot assay was performed for the quantification of Spike-specific T-cell response. Results were compared with those obtained in a cohort of healthy subjects. In a subset of patients, humoral and T-cell responses against delta variant were also evaluated. Less than 20% of transplanted subjects developed a positive humoral and cell-mediated response after complete vaccination schedule. Overall, median levels of immune response elicited by vaccination were significantly lower with respect to controls in SARS-CoV-2 naïve transplant, but not in SARS-CoV-2 recovered transplanted patients. Additionally, a significant impairment of both humoral and cell-mediated response was observed in mycophenolate-treated patients. Positive delta-SARS-CoV-2 NT Abs levels were detected in almost all the SARS-CoV-2 recovered subjects but not in previously uninfected patients. Our study supports previous observations of a low level of seroconversion after vaccination in transplanted patients.

Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients.

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Distress Syndrome: An Italian Society for Cardiac Surgery Report.

An increased need of extracorporeal membrane oxygenation (ECMO) support is going to become evident as treatment of SARS-CoV-2 respiratory distress syndrome. This is the first report of the Italian Society for Cardiac Surgery (SICCH) on preliminary experience with COVID-19 patients receiving ECMO support. Data from 12 Italian hospitals participating in SICCH were retrospectively analyzed. Between March 1 and September 15, 2020, a veno-venous (VV) ECMO system was installed in 67 patients (94%) and a veno-arterio-venous ECMO in four (6%). Five patients required VA ECMO after initial weaning from VV ECMO. Thirty (42.2%) patients were weaned from ECMO, while 39 (54.9%) died on ECMO, and six (8.5%) died after ECMO removal. Overall hospital survival was 36.6% (n = 26). Main causes of death were multiple organ failure (n = 14, 31.1%) and sepsis (n = 11, 24.4%). On multivariable analysis, predictors of death while on ECMO support were older age (p = 0.048), elevated pre-ECMO C-reactive protein level (p = 0.048), higher positive end-expiratory pressure on ventilator (p = 0.036) and lower lung compliance (p = 0.032). If the conservative treatment is not effective, ECMO support might be considered as life-saving rescue therapy for COVID-19 refractory respiratory failure. However warm caution and thoughtful approaches for timely detection and treatment should be taken for such a delicate patients population.

Should we perform heart retransplantation in early graft failure?

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure (n = 11) or late graft failure (acute rejection: n = 2, transplant-related coronary artery disease: n = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than (n = 11, all in early graft failure) or more than (n = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively (P = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.

Development and validation of a combined enzymatic-digestion/mass spectrometry assay for Tacrolimus quantitation in cardiac biopsies.

Recent studies report strategies for analysing immunosuppressive drugs in brain, liver and renal tissue, mostly in animals: we developed and validated a two steps combined enzymatic digestion/mass spectrometry assay to quantify Tacrolimus (TAC) in heart biopsies. Our aims were to avoid sample loss and sample contamination during the laboratory preparation, and to limit matrix effects in the electrospray ionization source (ESI) of the mass spectrometer. Enzymatic tissue digestion followed by a liquid-liquid drug extraction in the same vial of reaction allowed us to reach both our aims. The assay was assessed for selectivity, matrix effect, linearity, Lower Limit of Quantification (LLOQ) and Detection (LOD), accuracy and precision, according to the "Guideline on Bioanalytical Method Validation (EMA). A stable isotopically labelled (SIL) analogue (13CD2-TAC) was used as internal standard. The chromatographic separation of the analyte took 6 min. The observed linear range of quantification was 0.0162-0.520 ng in terms of TAC added to the biopsies (by 50 µL of the corresponding working solutions). The limit of detection and the lower limit of quantification (LLOQ) were 0.008 and 0.0162 ng, respectively. Both the mobile phases contained ammonium acetate and formic acid that promote the formation of ammoniated precursor ions that can be easily fragmented ([M + NH4]+, TAC m/z 821.3; 13CD2-TAC m/z 824.3). The calibration curves were generated by plotting analyte-to-internal standard peak area ratios versus TAC amount (ng) added to the biopsies, and using a weighted (1/x) linear regression. Curves were not forced to pass through the origin. Swine hearts were employed as blank matrix for all the analytical method validation procedures but, after approval by the ethics committee (by "Fondazione IRCCS Policlinico San Matteo": Protocol 20190032933), TAC was also quantified in endomyocardial biopsies from informed and consenting heart transplant patients. The study was funded by Fondazione IRCCS Policlinico San Matteo (RC08017617), as a part of the clinical studies on the maintenance of immunosuppressive therapy in cardiac transplant patients. Tacrolimus concentrations in patients biopsies were expressed as ratio between the detected amount of TAC (ng) in the tissue and the weight of the tissue itself (mg).

An experimental model of veno-venous arterial extracorporeal membrane oxygenation.

INTRODUCTION: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. AIM: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump-driven circuit. METHODS: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. RESULTS: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. CONCLUSION: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.

Long-Term Effects of the Replacement of Calcineurin Inhibitors With Everolimus and Mycophenolate in Patients With Calcineurin Inhibitor-Related Nephrotoxicity.

BACKGROUND: There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. METHODS: Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), without evidence of proteinuria, and in whom CNI therapy was replaced by everolimus, were analyzed. At the time of CNI withdrawal, clinical parameters, echocardiographic data, blood tests of renal function, and monitoring of adverse events were recorded. The median follow-up period was 5 years ± 28 months. RESULTS: In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. CONCLUSIONS: A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.