[Venoarterial extracorporeal membrane oxygenation: from evidence to clinical practice]. / Il supporto della circolazione extracorporea nelle emergenze cardiologiche: evidenze scientifiche e pratica clinica.

Mortality for cardiogenic shock is still high despite optimal pharmacological therapy. Therefore, active mechanical circulatory support devices are increasingly used; venoarterial extracorporeal membrane oxygenation (VA-ECMO) enables full circulatory and respiratory support. However, recent data show that in patients with infarct-related shock unselected early use of VA-ECMO does not improve survival and is associated with major bleeding and peripheral ischemic complications. Nowadays, waiting for the results of definitive randomized controlled trials, the main indication for ECMO utilization is in selected patients with cardiac arrest, in those with shock for advanced heart failure refractory to conventional therapy, in those with fulminant myocarditis, in patients candidate for heart transplant or ventricular assistance, especially in presence of respiratory insufficiency and severe biventricular dysfunction. An important recommendation is its utilization in specialized, high-volume centers in the setting of hub and spoke hospitals.

Clinical governance of patients with acute coronary syndromes.

AIMS: Using the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy. METHODS AND RESULTS: Administrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852-7867) ACS patients were admitted and 5107 were enrolled-i.e. a consecutive index of 69.6% (95% CI 64.9-74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7-24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40-0.89) and an adjusted NNT of 65 (95% CI: 44-250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7-71.4%), HR of 0.50 (95% CI: 0.38-0.66), and NNT of 98 (95% CI: 79-145). CONCLUSION: A comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery. REGISTRATION: ClinicalTrials.Gov ID NCT04255537.

Acute Coronary Syndromes and SARS-CoV-2 Infection: Results From an Observational Multicenter Registry During the Second Pandemic Spread in Lombardy.

Background: COVID-19 had an adverse impact on the management and outcome of acute coronary syndromes (ACS), but most available data refer to March-April 2020. Aim: This study aims to investigate the clinical characteristics, time of treatment, and clinical outcome of patients at hospitals serving as macro-hubs during the second pandemic wave of SARS-CoV-2 (November 2020-January 2021). Methods and Results: Nine out of thirteen "macro-hubs" agreed to participate in the registry with a total of 941 patients included. The median age was 67 years (IQR 58-77) and ST-elevation myocardial infarction (STEMI) was the clinical presentation in 54% of cases. Almost all patients (97%) underwent coronary angiography, with more than 60% of patients transported to a macro-hub by the Emergency Medical Service (EMS). In the whole population of STEMI patients, the median time from symptom onset to First Medical Contact (FMC) was 64 min (IQR 30-180). The median time from FMC to CathLab was 69 min (IQR 39-105). A total of 59 patients (6.3%) presented a concomitant confirmed SARS-CoV-2 infection, and pneumonia was present in 42.4% of these cases. No significant differences were found between STEMI patients with and without SARS-CoV-2 infection in treatment time intervals. Patients with concomitant SARS-CoV-2 infection had a significantly higher in-hospital mortality compared to those without (16.9% vs. 3.6%, P < 0.0001). However, post-discharge mortality was similar to 6-month mortality (4.2% vs. 4.1%, P = 0.98). In the multivariate analysis, SARS-CoV-2 infection did not show an independent association with in-hospital mortality, whereas pneumonia had higher mortality (OR 5.65, P = 0.05). Conclusion: During the second wave of SARS-CoV-2 infection, almost all patients with ACS received coronary angiography for STEMI with an acceptable time delay. Patients with concomitant infection presented a lower in-hospital survival with no difference in post-discharge mortality; infection by itself was not an independent predictor of mortality but pneumonia was.

BMPR2 mutations and response to inhaled or parenteral prostanoids: a case series.

Whether mutations in the BMPR2 gene may influence the response to PAH-specific therapies has not yet been investigated. In this study, in 13 idiopathic, heritable or anorexigen-associated PAH patients, in whom treatment escalation was performed by adding a prostanoid, a greater haemodynamic improvement was observed in BMPR2-negative than in BMPR2-positive patients.

[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.

Risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy.

BACKGROUND: Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models. METHODS: We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months. RESULTS: Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm-5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm-5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel's C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model's predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH. CONCLUSIONS: Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters.

Has hyperglycemia a different prognostic role in STEMI patients with or without diabetes?

BACKGROUND AND AIMS: Hyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled. We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact. METHODS: and Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5-2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2-3.4, p = 0.01). CONCLUSION: Hyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated.

Post-ROSC peripheral perfusion index discriminates 30-day survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication after an out-of-hospital cardiac arrest (OHCA) remains a challenge. The peripheral-derived perfusion index (PI) is a simple and non-invasive way to assess perfusion. We sought to assess whether the PI was able to discriminate the prognosis of patients resuscitated from an OHCA. METHODS: All the reports generated by the manual monitor/defibrillator (Corpuls 3 by GS Elektromedizinische Geräte G. Stemple GmbH, Germany) used for all the OHCAs who achieved ROSC treated by our Emergency Medical Service from January 2015 to December 2018 were reviewed. The mean PI value of each minute after ROSC was automatically provided by the device and the mean value of 30 min of monitoring (MPI30) was calculated. Pre-hospital data were collected according to the Utstein 2014 recommendations. RESULTS: Among 1,909 resuscitation attempts, ROSC was achieved in 346 and it was possible to calculate an MPI30 in 164. MPI30 was higher in the patients who survived at 30 days [1.6 (95% CI 1.2-2.1) vs 1 (95% CI 0.8-1.3), p = 0.0017]. At the multivariable Cox regression model, after correction for shockable rhythm, witnessed status, bystander CPR, age, and blood pressure, MPI30 was found to be an independent predictor of both 30-day mortality [RR 0.83 (95% CI 0.69-0.99), p = 0.036] and 30-day mortality or poor neurologic outcome [RR 0.85 (95% CI 0.72-0.99), p = 0.04]. Overall 30-day survival with good neurologic outcome was significantly different in the three tertiles [T1: 0.1-0.8; T2: 0.9-1.8 and T3: 1.82-7.8, log-rank p = 0.007]. CONCLUSION: The post-ROSC peripheral perfusion index was found to be an independent predictor of 30-day mortality or poor neurologic outcome. It could help prognostication in OHCA patients.

Leptin affects the inflammatory response after STEMI.

Leptin is an adipose tissue-derived hormone primarily involved in the regulation of food intake. Leptine has been shown to have a much broader role than just regulating body weight and appetite in response to food intake: among the others, it has been associated with increased ROS production and inflammation, factors involved in the restoration of an effective myocardial reperfusion after myocardial revascularization. Our study, to our best knowledge, is the first showing a direct relationship between leptin serum levels, inflammatory mediators of the ischemia reperfusion damage and effective myocardial reperfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Our findings suggest that leptin serum levels are directly associated with the inflammatory response during an acute myocardial infarction and may have a role in risk stratification in this clinical setting.

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.

Percutaneous Coronary Intervention Techniques for Bifurcation Disease: Network Meta-analysis Reveals Superiority of Double-Kissing Crush.

BACKGROUND: Provisional T-stenting (PS) is generally recommended to treat patients with coronary bifurcation disease (CBD) percutaneously, but PS may not fit all complex bifurcation anatomies. Therefore, several types of up-front 2-stent techniques have been described. We aimed to identify the best percutaneous coronary intervention (PCI) technique to manage patients with CBD. METHODS: We systematically reviewed randomized controlled trials (RCTs) including patients undergoing CBD PCI which included several types of PCI techniques-PS, double-kissing (DK) crush, T-stenting and protrusion, culotte, dedicated bifurcation stents, crushing, and T-stenting-and we compared device-oriented clinical events (DOCEs), a composite of cardiac death, target-vessel myocardial infarction, stent thrombosis, and target-lesion or target-vessel revascularization, in a network meta-analysis. We included 26 RCTs, leading to a pooled population of 10,339 patient-years and a total of 1229 DOCEs. RESULTS: The DK-crush technique was associated with the lowest DOCE rate, with a relative risk of 0.62 (95% CI 0.42-0.92) compared with the PS technique. DK-crush had the highest probability (model likelihood 90.2%, area under the cumulative ranking curve 98.0%) of being the best technique among those explored to reduce DOCEs in patients receiving CBD PCI. CONCLUSIONS: When a 2-stent strategy is considered in a patient with CBD, the DK-crush technique reduces DOCEs compared with other bifurcation techniques based on all available RCTs.