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To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR ≥ 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR ≥ 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77–4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90).

The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme (reference: ANR-15-RHUS-0004), by the French PIA project 'Lorraine Université d'Excellence' (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. Aims: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. Methods and results: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B-lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right-sided, left-sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all-cause death or HF-related hospitalization. Two hundred and thirty-three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B-line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B-lines (20.6 ± 11), followed by left-sided (19.7 ± 11.6) and right-sided (13.5 ± 9.8). B-lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6-40)]. B-lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01-1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B-line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01-1.07), P = 0.014], with a 4% increase risk per B-line added. B-lines correlated significantly with CA125 (R = 0.30, P = 0.001). Conclusions: Lung ultrasound supports the diagnostic work-up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short-term events.

Background Left ventricle assist devices (LVAD) are an option in end stage heart failure (HF) as bridge to or alterative to heart transplantation. Adequate compensation of patient is key to obtain a good outcome. We report two cases of Impella 5.0 bridge to LVAD in patients with cardiogenic shock (CS) in which intra-aortic balloon pump (IABP) failed to obtain hemodynamic stability. Case series A) A 60 years old man developed CS after anterior myocardial infarction treated with primary PCI of left main coronary artery. At presentation patient was hypotensive with signs of hypoperfusion and pulmonary congestion: systemic blood pressure (SBP) 80/60 mmHg despite inotropic drugs, blood lactates 4 mmol/l, urine output of last 6 hours 0,4 ml/kg/h (INTERMACS 2). Echocardiography showed severe left ventricle disfunction with LVEF 15%, severe mitral regurgitation (MR) and sPAP 45 mmHg. Therefore, IABP was implanted. Right heart catheterization (RHC) showed pulmonary hypertension and high filling pressure with reduced cardiac output and increased pulmonary vascular resistance (mPAP 39 mmHg, CPWP 28 mmHg, CO 3 l/min, PVR 3.7 uW, PAPi 2.8); X-ray chest showed persistence of pulmonary congestion. After 9 days on IABP, patient underwent Impella 5.0 implant through right axillary artery as bridge to durable LVAD. Pulmonary artery catheter (PAC) monitoring showed reduction of pulmonary hypertension with mPAP 35 mmHg and CPWP 17 mmHg and chest X-ray documented improvement of lung congestion. Bedside rehabilitation was started. Two weeks later patient underwent LVAD HM3 implantation as destination therapy. The patient was discharge home on post-operative day 55. B) After subacute myocardial infarction with three-vessels disease, a 53 y.o. man developed severe congestive HF with severe left ventricular disfunction and was referred to our institution for evaluation. RHC showed pulmonary hypertension with pre-capillary component not reversible after enoximone test, contraindicating heart transplantation. Therefore, patient was candidate to receive LVAD as bridge strategy. Echocardiography at admission showed dilated and hypokinetic left ventricle (EDV 200 ml, LVEF 17% severe MR, sPAP 60 mmHg) and dilated and hypokinetic RV. During hospitalization the patient experienced CS with SBP 62/45 mmHg, 6-hours urine output of 1,4 ml/kg/h and blood lactates 8.3 mmol/l (INTERMACS 1) so femoral IABP was implanted. RHC was repeated both without IABP support (mPAP 37 mmHg, PCWP 28 mmHg, CO 1.4 l/min, CI 0.9 l/min/m2) and with IABP support (mPAP 32 mmHg, PCWP 18 mmHg, CO 2.15 l/min, CI 1.4 l/min/m2). During the following stay he developed S. Aureus sepsis requiring prolonged antibiotic therapy. Expecting a long time before LVAD, axillary Impella 5.0 was implanted in order to unload the LV and allow early patient mobilization. Subsequent PAC monitoring showed improvement of pulmonary hypertension and cardiac index (mPAP 24 mmHg, PCWP 9 mmHg, CO 5.1 l/min with Impella flow 4.2 l/min, CI 3.2 l/min/m2). After 11 days, patient received LVAD HVAD with uneventful course and was discharged on post-operative day 22. Conclusions Impella 5.0 is a surgically implanted intravascular microaxial blood pump that delivers up to 5 l/min of blood from LV to aorta, leading to improved perfusion and more efficient LV unloading. In patients with CS this can help to obtain better decongestion, RV recovery, and favorable preconditioning before LVAD implant. Moreover, axillary access allows better patient mobilization preventing cachexia after long time hospitalization.

Aims to describe epidemiology, clinical characteristics and treatment modalities adopted in a cohort of patients eligible for cardiac transplantation or left ventricular assist device implantation admitted for cardiogenic shock atour center. Secondly, to identify clinical risk factors for in-hospital mortality to evaluate the role of surgical treatment options (cardiac transplantation and L-VAD implant) as modifiers of prognosis in this patient population. Methods We retrospectively identified discharge charts containing ICD-9 codes of cardiogenic shock (785.51) and IABP implantation (37.61) at our center in the period 2016-2021. Patients were considered eligible in the age rage 18-70 years old, according to the upper age limit of cardiac transplant and LVAD program. Patients presenting with cardiogenic shock after cardiac surgery, cardiogenic shock secondary to acute pulmonary embolism and acute aortic syndrome or patients needing IABP placement as preventive support for high-risk percutaneous or surgical myocardial revascularization procedures were excluded. Results 163 patients were included in the study (mean age 56 years, 80% male). In this cohort of patients, the most common etiologies were represented by coronary artery disease (64% of patients) and cardiomyopathy (26% of patients), mostly idiopathic dilated forms followed by hypertrophic cardiomyopathy and cardiac amyloidosis. The remaining 10% of patients were affected by other forms of cardiac disease (which included acute myocarditis and cancer therapy-related CV toxicity). Diabetes mellitus and hypertension were the most common CV risks factors. Acute coronary syndrome was the underlying cause in 45% patients presenting with cardiogenic shock, while 56% of CS cases were due to acute decompensated heart failure not in the setting of ACS. Most patients (80%) were supported with IABP alone, while 10% needed cardiocirculatory support with ECMO. Regarding outcome, in-hospital mortality for CS was 30% (48 patients), while 36 patients (22%) underwent surgical treatment of heart failure with cardiac transplantation (21 patients) or L-VAD implantation (15 patients). Predictors of in-hospital mortality at univariate analysis were older age, lower eGFR at the time of shock (p=0,0001), persistence of elevated blood lactates > 2 at CS presentation and at 24 hours (p=0,0001), and a failure to improve in renal impairment at 24 hours. Multivariate analysis identified lower eGFR and high lactates at 24 hours as independent risk factors for in-hospital mortality. Conclusions cardiogenic shock still remains a high-mortality condition. Mechanical circulatory support could provide stabilization and bridge to urgent cardiac transplantation and L-VAD implantation in order to improve prognosis. There is still need for diagnostic and therapeutic protocols standardized to improve the prognostic stratification and survival of patients with cardiogenic shock.

A 49-year-old man without cardiovascular risk factors, recently diagnosed of asthma and rino-sinusal polyposis, entered the Emergency Department for chest pain, shortness of breath and non-productive cough. The patient was in stable conditions. Laboratory exams showed eosinophilic leucocytosis (WBC 33.000/sqmm, 60% eosinophils) and a mild elevation of C-reactive protein (CRP 2,2 mg/dL). ECG showed a sinus rhythm with flat T-waves in the antero-lateral leads. Troponin values were high but not suggestive of acute myocardial damage (9900 - 9700 ng/L). Echocardiography showed normal biventricular volumes with moderately depressed left ventricular ejection fraction (40%), hypokinesia of the antero-lateral wall in the mid-apical segments and mild pericardial effusion. During the hospital stay he developed progressive respiratory failure, and he was transferred to a tertiary center to perform an endomyocardial biopsy (EMB) in the suspicion of acute myocarditis. EMB showed multifocal interstitial and sub-endocardial inflammatory infiltrates (predominantly eosinophils) with foci of myocellular damage, small vessels wall inflammation with hypertrophy of the muscular tunica. The overall picture was consistent with diffuse moderate eosinophilic myocarditis with small vessels vasculitis. The right heart cath performed in the same procedure and during diuretic therapy showed a normal hemodynamic profile (RAP 5 mmHg, PCWP 13 mmHg, CI 3,7 L/min/sqm). The patient was treated with high dose steroids, first intravenously (methylprednisolone 125 mg/day for three days), then orally (prednisone 80 mg/day) in slow decalage until a maintenance dose of 12.5 mg daily. The recent-onset of asthma with hyper-eosinophilia and rhino-sinus-bronchial syndrome in the light of the present cardiac condition was consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Chest CT showed two areas of ground glass at the left superior and right superior lobes. Other potential haematological and infective causes of hyper eosinophilia and viral causes of myocarditis were ruled out. After the treatment, his clinical conditions improved, ECG was completely normalized, left ventricular systolic function improved (LVEF 50%) and eosinophil count was significantly reduced (Eosinophils 830/sqmm, 8,9%), whereas CT showed resolution of the lung infiltrates. One month after discharge, the patient was still asymptomatic. Cardiac MRI showed normal biventricular ejection fraction (LVEF 55%) with circumferential subendocardial fibrosis involving only the left ventricle. EMB showed a complete resolution of the inflammatory infiltrates and of the vasculitic aspects. Eosinophil count was elevated (5660/sqmm, 36%). Therefore, steroidal dose was raised to 50 mg/day. After rheumatologic evaluation, a steroidal sparing strategy with cyclophosphamide and anti-IL5 antibody Mepolizumab was adopted, with good laboratory response. Three months later, cardiac MRI showed no signs of active disease. No further EMB was scheduled. Through the presentation of this unusual cause of acute myocarditis, we want to underscore the importance of an early referral to a tertiary level center of patients with suspected myocarditis and reduced systolic function and the usefulness of histology to guide medical therapy in specific forms of myocarditis that can lead to a potential complete recovery.

Background Temporary mechanical circulatory support (MCS) could provide stabilization and improve prognosis in selected patients with cardiogenic shock (CS). Intra-aortic balloon pump (IABP) is a common percutaneous MCS device, characterized by wide availability, easy deployment and low complication rate. Despite its use in CS caused by acute myocardial infarction has been discouraged based on available evidence, recent data have renewed the interest in IABP as bridge to heart replacement therapy (HRT; heart transplantation or durable LVAD implant) in patients with cardiogenic shock complicating acutely decompensated chronic heart failure. We sought to review our experience with IABP support in this population eligible for HRT at a large-volume transplant center. Methods We retrospectively reviewed all adult patients (> 18 years old) who received IABP at our center between 2016 and 2021. We included patients with chronic heart failure with reduced ejection fraction (LVEF < 40% for at least 3 months) eligible for heart replacement therapy (i.e. < 70 years old). Primary endpoint was IABP success defined as weaning to discharge or successful bridge to HRT without need for MCS escalation. In addition, in-hospital mortality without HRT and MCS complications were assessed. Results Study population consisted of 49 patients with mean age of 54±9 years, 84% of whom were male. Etiology was non-ischemic dilated cardiomyopathy in 72% of patients and mean LVEF was 19±5%. 12 patients (24%) were already listed for heart transplantation. 26 patients (53%) developed cardiogenic shock during hospitalization for acutely decompensated heart failure, while the others presented CS upon admission. IABP success was achieved in 32 (65%) of patients, of whom 13 (39%) were bridged to heart transplantation, 6 (18%) to durable LVAD, while 13 (43%) were weaned from support and discharged. 11 patients (22%) died without MCS upgrade or HRT, including one death occurring 18 days after IABP weaning. 6 patients (12%) required escalation of mechanical circulatory support: 5 with extracorporeal membrane oxygenator (ECMO), 2 of whom were transplanted, and 1 with axillary-implanted Impella 5.0 as effective bridge to durable LVAD. In-hospital mortality without HRT was 28%. Median duration of IABP support was 8 days (0-107). 66% of patients were treated with at least one and 12% with two or more inotropes. Complications occurred in 4 (9%) patients in IABP group, including 3 cases of limb ischemia without sequelae and one fatal bleeding not related to insertion site. Ischemic and bleeding complications were found in 4 out of 5 ECMO-supported patients. Among demographic and laboratory characteristics assessed at baseline and after 24 hours from shock, persistence of increased lactates (>2 mmol/l) at 24 hours and number of inotropic drugs were independently associated with both IABP failure and mortality. Conclusions In patients with cardiogenic shock complicating chronic heart failure, IABP appears a safe and effective bridge strategy to heart replacement therapy with favorable outcomes and acceptable complication rates. Persistence of markers of hypoperfusion and increased need for cardioactive drugs are associated with worse outcomes and should trigger evaluation for MCS escalation. More studies are needed to fully characterize the role and timing of IABP support in this clinical scenario.

The impact of increasing temperatures on renal function in heart failure (HF) outpatients has never been specifically analyzed.We retrieved creatinine and estimated glomerular filtration rate (eGFR) values of all HF outpatients followed at a HF clinic and temperature data from 2002 to 2021. For each patient and each year we averaged values of creatinine, eGFR and monthly temperatures during summer and the rest of the year.The study cohort included 2167 HF patients undergoing 25,865 elective visits, with a median of 14 visits for each patient (interquartile range 7-23). At the first visit, patients (70% men) had an age of 67 ± 13 years, and a left ventricular ejection fraction of 35 ± 14%. Creatinine was 1.25 ± 0.51 mg/dL, and eGFR was 65 ± 25 mL/min/1.73 mThe magnitude of temperature elevation during summer has increased over 20 years. This elevation correlates with the decline in renal function during summer. This might be an example of how global warming is affecting human health.

Purpose Wire-based coronary physiology pullback performed before percutaneous coronary intervention (PCI) discriminates coronary artery disease (CAD) distribution and extent, and is able to predict functional PCI result. No research investigated if quantitative flow ratio (QFR)–based physiology assessment is able to provide similar information. Methods In 111 patients (120 vessels) treated with PCI, QFR was measured both before and after PCI. Pre-PCI QFR trace was used to discriminate functional patterns of CAD (focal, serial lesions, diffuse disease, combination). Functional CAD patterns were identified analyzing changes in the QFR virtual pullback trace (qualitative method) or after computation of the QFR virtual pullback index (QVPindex) (quantitative method). QVPindex calculation was based on the maximal QFR drop over 20 mm and the length of epicardial coronary segment with QFR most relevant drop. Then, the ability of the different functional patterns of CAD to predict post-PCI QFR value was tested. Results By qualitative method, 51 (43%), 20 (17%), 15 (12%), and 34 (28%) vessels were classified as focal, serial focal lesions, diffuse disease, and combination, respectively. QVPindex values >0.71 and ≤0.51 predicted focal and diffuse patterns, respectively. Suboptimal PCI result (post-PCI QFR value ≤0.89) was present in 22 (18%) vessels. Its occurrence differed across functional patterns of CAD (focal 8% vs. serial lesions 15% vs. diffuse disease 33% vs. combination 29%, p=0.03). Similarly, QVPindex was correlated with post-PCI QFR value (r=0.62, 95% CI 0.50–0.72). Conclusion Our results suggest that functional patterns of CAD based on pre-PCI QFR trace can predict the functional outcome after PCI. Clinical Trial Registration ClinicalTrials.gov, number NCT02811796. Date of registration: June 23, 2016.

Background: Coronary angiography is the gold standard for cardiac allograft vasculopathy (CAV) diagnosis, but it usually detects the disease at an advanced stage. We investigated the role of quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, in predicting CAV development in heart transplant recipients. Methods: Consecutive heart transplant recipients with no evidence of angiographic CAV at baseline coronary angiography were retrospectively included between January 2010 and December 2015, and QFR computation was performed. The relationship between vessel QFR and the occurrence of angiographic vessel-related CAV ( ≥ 50% stenosis) was assessed. Results: One hundred forty-three patients were included and QFR computation was feasible in 241 vessels. The median value of QFR at baseline coronary angiography was 0.98 (interquartile range, 0.94–1.00). During a median follow-up of 6.0 years (interquartile range, 4.6–7.8 years), vessel-related CAV occurred in 25 (10.4%) vessels. Receiver-operating characteristic curve analysis identified a QFR best cutoff of ≤ 0.95 (area under the curve, 0.81 [95% CI, 0.71–0.90]; P ≤ 0.95 was associated with an increased risk of vessel-related CAV (adjusted hazard ratio, 20.87 [95% CI, 5.35–81.43]; P ≤ 0.95 in at least 2 vessels was associated with higher incidence of cardiovascular death or late graft dysfunction (71.4% in recipients with 2–3 vessels affected versus 5.1% in recipients with 0–1 vessels affected, P Conclusions: In a cohort of heart transplant recipients, QFR computation at baseline coronary angiography may be a safe and reliable tool to predict vessel-related CAV and clinical outcomes at long-term follow-up.

Myocardial fibrosis is a common feature of several heart diseases. The progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may trigger a vicious cycle that leads to persistent structural and functional alterations of the myocardium. Some drugs (like renin–angiotensin–aldosterone system inhibitors) have been shown to reduce extracellular matrix deposition, but no primarily anti-fibrotic medications are currently used to treat patients with heart failure (HF). Pirfenidone is an oral antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. Although its exact mechanism of action is not fully understood, pirfenidone might reduce the expression of profibrotic factors such as transforming growth factor-β (TGF-β), and proinflammatory cytokines, like tumor necrosis factor-α (TNF-α), interleukin (IL)-4, and IL-13, which could modulate the inflammatory response and inhibit collagen synthesis in lung tissue. There is some evidence that pirfenidone has antifibrotic activity in various animal models of cardiac disease. Furthermore, the positive results of the PIROUETTE trial, evaluating pirfenidone in patients with HF with preserved ejection fraction, have been very recently announced. This review summarizes the data about pirfenidone as a potential cardioprotective treatment.

Objectives The aim of this study was to investigate the potential role of post–percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) measurements to predict clinical outcomes in patients with successful PCI. Background The prognostic value of QFR measured immediately after PCI has not been prospectively investigated. Methods Patients undergoing complete revascularization with successful PCI and stent implantation were eligible for acquisition of projections for QFR computation. At the end of the procedure, 2 angiographic projections for each vessel treated with PCI were acquired. Computation of QFR was performed offline by an independent core laboratory. The primary outcome was the vessel-oriented composite endpoint, defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. Results Seven hundred fifty-one vessels in 602 patients were analyzed. The median value of post-PCI QFR was 0.97 (interquartile range: 0.92 to 0.99). Lesion location in the left anterior descending coronary artery, baseline SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score, lesion length, and post-PCI diameter stenosis were found to be predictors of lower post-PCI QFR. Altogether, 77 events were detected in 53 treated vessels (7%). Post-PCI QFR was significantly lower in vessels with the vessel-oriented composite endpoint during follow-up, compared with those without it (0.88 [interquartile range: 0.81 to 0.99] vs. 0.97 [interquartile range: 0.93 to 0.99], respectively; p Conclusions Lower values of QFR after complete and successful revascularization predict subsequent adverse events (Angio-Based Fractional Flow Reserve to Predict Adverse Events After Stent Implantation [HAWKEYE]; NCT02811796)

Pirfenidone (PFD) slows the progression of idiopathic pulmonary fibrosis (IPF) by inhibiting the exaggerated fibrotic response and possibly through additional mechanisms, such as anti-inflammatory effects. PFD has also been evaluated in other fibrosing lung diseases. Myocardial fibrosis is a common feature of several heart diseases and the progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may trigger a vicious cycle that leads to persistent structural and functional alterations of the myocardium. No primarily antifibrotic medications are used to treat patients with heart failure. There is some evidence that PFD has antifibrotic actions in various animal models of cardiac disease and a phase II trial on patients with heart failure and preserved ejection fraction has yielded positive results. This review summarises the evidence about the possible mechanisms of IPF and modulation by PFD, the main results about IPF or non-IPF interstitial pneumonias and also data about PFD as a potential protective cardiac drug.

Severe tricuspid regurgitation remains a challenging heart-valve disease to effectively treat with high morbidity and mortality at mid-term. Currently guideline-directed medical treatment is limited to escalating dose of diuretics, and the rationale and timing of open-heart surgery remains controversial. Emerging percutaneous therapies for severe tricuspid regurgitation continue to show promising results in early feasibility studies. However, randomized trial data is lacking. Additionally, many patients are deemed unsuitable for these emerging therapies due to anatomical or imaging constraints. Given the technical simplicity of the bicaval valve implantation (CAVI) technique compared to other transcatheter devices, CAVI is postulated as a suitable alternative for a wide variety of patients affected with severe+ tricuspid regurgitation. In this review we illustrate the current evidence and ongoing uncertainties of CAVI, focusing on the novel CAVI-specific devices.

BackgroundCirculating Neprilysin (sNEP) has emerged as a potential prognostic biomarker in heart failure (HF). In PARAGON-HF benefit of sacubitril/valsartan was only observed in patients with left ventricular ejection fraction (LVEF) ≤57%. We aimed to assess the prognostic value of sNEP in outpatients with HF and LVEF >57%, in comparison with patients with LVEF ≤57%.MethodsConsecutive HF outpatients were included from May-2006 to February-2016. The primary endpoint was the composite of all-cause death or HF hospitalization and the main secondary endpoint was the composite of cardiovascular death or HF hospitalization. For the later competing risk methods were used.ResultssNEP was measured in 1428 patients (age 67.7±12.7, 70.3% men, LVEF 35.8% ±14), 144 of which had a LVEF >57%. sNEP levels did not significantly differ between LVEF groups (p = 0.31). During a mean follow-up of 6±3.9 years, the primary endpoint occurred in 979 patients and the secondary composite endpoint in 714 (in 111 and 84 of the 144 patients with LVEF >57%, respectively). sNEP was significantly associated with both composite endpoints. Age- and sex- adjusted Cox regression analyses showed higher hazard ratios for sNEP in patients with LVEF >57%, both for the primary (HR 1.37 [1.16–1.61] vs. 1.04 [0.97–1.11]) and the secondary (HR 1.38 [1.21–1.55] vs. 1.11 [1.04–1.18]) composite endpoints.ConclusionssNEP prognostic value in patients with HF and LVEF >57% outperforms that observed in patients with lower LVEF. Precision medicine using sNEP may identify HF patients with preserved LVEF that may benefit from treatment with sacubitril/valsartan.

Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy.In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence.The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.

Vasoplegic syndrome (VS) is associated with poor outcomes after heart transplantation (HT). Our aim was to determine whether SAC/VALS is associated with VS after HT. We retrospectively analyzed all consecutive HT performed in three centers between January 2017 and August 2018. VS was defined as vasopressor need (norepinephrine or epinephrine >.5 mcg/kg/min or vasopressin) for more than 24 hours to maintain a mean arterial pressure >70 mm Hg. Ninety-six recipients underwent HT in the study period: 60 elective HT with no LVAD, 5 elective HT on long term LVAD, and 31 emergent HT: 3 on long-term LVAD and 28 on temporary mechanical circulatory support. Fourteen patients were on SAC/VALS treatment at the time of transplant, and 82 were not. The global incidence of VS was 15.6%, with no significant differences between the groups (7.14% in with SAC/VALS vs 17.07% in no-SAC/VALS). In conclusion, in our small cohort SAC/VALS was not associated with VS development.

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), lack of ST-segment resolution (STR) is associated with poor prognosis at short- and long-term follow-up. The aim of this study was to evaluate the role of STR on very long-term outcomes in patients with STEMI treated with pPCI included in the EXAMINATION (Evaluation of the Xience-V Stent in Acute Myocardial Infarction) trial. Patients were stratified according to the presence of STR 50% and STR >= 70%, respectively. In both cases, this difference was mainly driven by a significant increase in the rate of all-cause death and any revascularization. After multivariable adjustment, STR < 70%, but not STR < 50%, resulted as a 5-year independent predictor of POCE (adjusted HR 1.338, 95% CI 1.008 to 1.778, p = 0.044). In conclusion, in patients with STEM!, the evaluation of 70% STR after pPCI provides independent prognostic information at 5-year follow-up and it can be used to identify patients at high risk of very long-term cardiovascular events. (C) 2018 Elsevier Inc. All rights reserved.

Objective: We sought to demonstrate that the combination of a local vasodilator (verapamil), modern materials, patent hemostasis, and intravenous anticoagulant only in the case of percutaneous coronary intervention, as compared to default heparin administration after sheath insertion, may optimize a combined endpoint, including radial artery oc­clusion (RAO), radial artery spasm (RAS), and access site complication. Methods: This is a prospective, single-center, double-blind randomized trial. Overall, 418 patients undergoing a transradial approach (TRA) for coronary procedures were randomized 1: 1 to receive intraradial verapamil (5 mg) or heparin (5,000 IU) after a 6-Fr sheath insertion. The primary outcome was the 24-h occurrence of RAO (ultrasound confirmation), access site complication, and RAS requiring the bailout administration of vasodilators. Results: The combined primary outcome occurred in 127 (30%) patients. It was significantly lower in patients randomized to verapamil as compared to others (26 vs. 35%, p = 0.03). This was mainly due to a significant reduction in RAS (3 vs. 10%, p = 0.006). The 24-h and 30-day occurrence of RAO did not differ between the study groups. Conclusion: Local administration of verapamil versus heparin reduces RAS, without increasing RAO, which appears to be strictly related to radial artery diameter and hemostasis time.

BACKGROUND No study has evaluated the clinical consequences of stent fracture (SF) detected during the index percutaneous coronary intervention (PCI). Thus, we sought to investigate the relationship between SF detected during PCI and clinical outcome.Methods and Results:We consecutively enrolled 832 patients with SF-predisposing factors undergoing 2nd-generation drug-eluting stent implantation and enhanced stent visualization (ESV) system evaluation to detect SF at index PCI. The primary endpoint was a 9-month device-oriented endpoint (DOCE, including cardiac death, target vessel myocardial infarction, and target lesion revascularization). We observed 136 SF in 115 patients (14% of study population). SF I-II was present in 78 patients (68% of patients with SF), and SF III-IV occurred in 37 patients (32%). DOCE at 9 months occurred in 135 patients (16% of the overall population). There was a significant difference in DOCE occurrence between the 3 groups (P=0.006 at log-rank), driven by the SF III-IV group (P=0.001 vs. no SF group, and P=0.01 vs. SF I-II group). In 23 cases of SF III-IV (62%) a further stent was implanted. DOCE occurrence was significantly higher in patients with "untreated" type III-IV SF as compared with the "treated" ones (9% vs. 79%, P

The aim of this study was to investigate the potential role of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) measurements to predict clinical outcomes in patients with successful PCI.The prognostic value of QFR measured immediately after PCI has not been prospectively investigated.Patients undergoing complete revascularization with successful PCI and stent implantation were eligible for acquisition of projections for QFR computation. At the end of the procedure, 2 angiographic projections for each vessel treated with PCI were acquired. Computation of QFR was performed offline by an independent core laboratory. The primary outcome was the vessel-oriented composite endpoint, defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization.Seven hundred fifty-one vessels in 602 patients were analyzed. The median value of post-PCI QFR was 0.97 (interquartile range: 0.92 to 0.99). Lesion location in the left anterior descending coronary artery, baseline SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score, lesion length, and post-PCI diameter stenosis were found to be predictors of lower post-PCI QFR. Altogether, 77 events were detected in 53 treated vessels (7%). Post-PCI QFR was significantly lower in vessels with the vessel-oriented composite endpoint during follow-up, compared with those without it (0.88 [interquartile range: 0.81 to 0.99] vs. 0.97 [interquartile range: 0.93 to 0.99], respectively; p 0.001). Receiver-operating characteristic curve analysis identified a post-PCI QFR best cutoff of ≤0.89 (area under the curve 0.77; 95% confidence interval: 0.74 to 0.80; p 0.001). After correction for potential confounding factors, post-PCI QFR ≤0.89 was associated with a 3-fold increase in risk for the vessel-oriented composite endpoint (hazard ratio: 2.91; 95% confidence interval: 1.63 to 5.19; p 0.001).Lower values of QFR after complete and successful revascularization predict subsequent adverse events (Angio-Based Fractional Flow Reserve to Predict Adverse Events After Stent Implantation [HAWKEYE]; NCT02811796).

BACKGROUND: A 71-year-old woman had a scheduled optical coherence tomography (OCT) (ILUMIEN"; St. Jude Medical, St. Paul, MN, USA) follow-up two years after implantation of a 3.0×18 mm bioresorbable vascular scaffold (BVS) (Absorb"; Abbott Vascular, Santa Clara, CA, USA) in the proximal left anterior descending coronary artery. She had dyspnoea corresponding to New York Heart Association (NYHA) Class II. INVESTIGATION: Diagnostic angiography, OCT and fractional flow reserve (FFR) measurement. DIAGNOSIS: OCT showed a covered and embedded BVS (not yet fully resolved after 24 months) and a distal edge in-scaffold restenosis and diffuse disease with an FFR of 0.74. MANAGEMENT: The BVS edge stenosis and the segment with diffuse disease distal to the previously implanted BVS were treated with an additional Absorb BVS 3.0×28 mm overlapping with the BVS implanted two years earlier. Supplementary OCT showed a large intra-scaffold dissection proximal to the overlapping BVS segment; the dissection flap contained the previously implanted BVS.

Background— The nonculprit lesion (NCL) management in ST-segment–elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario. Methods and Results— The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n=31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n=45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3–4 days later) procedures ( r =0.98; 95% confidence interval, 0.96–0.99; mean difference, 0.004 [−0.027 to 0.34]). The inter-rater agreement was κ=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89–0.99). Finally, in cohort C, we identified 110 ST-segment–elevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value ≤0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2–4.5; P =0.01). Conclusions— In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment–elevation myocardial infarction patients.

Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF). HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, the prognostic role of NP in COPD patients remains unclear. The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients. We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients. Nine studies were considered for qualitative analysis for a total of 2788 patients. Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis. Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively). The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age). NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD.

BACKGROUND Nuisance bleeding is a major determinant of quality of life and drug discontinuation in patients on dual antiplatelet therapy (DAPT). However, no randomized trial has been focused on the impact of nuisance bleeding on quality of life. METHODS BATMAN is an investigator-driven, randomized, controlled, single-center, open trial (NCT02554006). Four hundred and forty-eight consecutive patients with indication to at least 6 months of DAPT were randomized to: i) multimodal counseling program focused on nuisance bleedings (interventional arm); ii) usual discharge process (control arm). The primary endpoint was the one-month health-related quality of life assessed by the EuroQol-5 Dimension (EQ-5D) visual analog scale (VAS) score. Secondary endpoints were EQ-5D at 1 and 6 months, EQ-5D VAS at 6 months, DAPT withdrawal, need of information regarding DAPT and/or nuisance bleedings, 6-month ischemic and bleeding adverse events. RESULTS The EQ5D-VAS was significantly higher in the interventional arm compared to the control arm at 1 and 6 months (81[74-88] vs. 73[64-80], p < 0.001 at 1 month; 82[76-88] vs. 74[65-81], p < 0.001 at 6 months). Patients in the interventional arm had also significantly lower pain/discomfort and anxiety/depression at the EQ-5D both at 1 and 6 months. Patients in the control arm withdrew DAPT significantly more (7 (3%) vs. 1 (0.4%), p = 0.03) and looked for information regarding DAPT and/or about nuisance bleeding more frequently than those in the interventional arm (178 (79%) vs.19 (8%), p < 0.001). CONCLUSIONS The systematic utilization of a multimodal counseling program improved quality of life and reduced the DAPT withdrawal rate in patients on DAPT.

Patients with high body mass index (BMI) seem to have better outcomes after percutaneous coronary intervention than normal-weight patients. However, contrasting results have been reported on the "obesity paradox" in patients presenting with ST-elevation myocardial infarction (STEMI). The aim of our study was to investigate the impact of BMI on mortality in the population enrolled in the Evaluation of the Xience-V stent in Acute Myocardial INfArcTION (EXAMINATION) trial. The EXAMINATION trial randomized 1,498 patients with STEMI to a bare-metal stent or an everolimus-eluting stent. In this substudy patients were stratified into 3 groups according to BMI values: normal (BMI < 25 kg/m(2)), overweight (BMI = 25 to 29.9 kg/m(2)), and obese (BMI 30 kg/m(2)). The coprimary end points were the all-cause and cardiac deaths among the groups at the 5-year follow-up. BMI was available in 1,421 patients, divided in 401 (28.2%) normal, 702 (49.4%) overweight, and 318 (22.4%) obese. Obese patients were younger (p = 0.012) compared with the other groups, but with a worse cardiovascular risk profile. They were more frequently female (p

Bioresorbable vascular scaffolds (BRS) represent a novel approach for coronary revascularization offering several advantages as compared to current generation DES, potentially reducing rate of late adverse events and avoiding permanent vessel caging. Nevertheless, safety concerns have been raised for an increased risk of scaffold thrombosis (ScT) in both early and late phases, probably related to a suboptimal scaffold implantation. In this context, the use of different imaging methodologies has been strongly suggested in order to guarantee an optimal implantation. We herein analyze the different imaging methodologies available to assess BRS after implantation and at follow-up.

Several studies suggested that chronic obstructive pulmonary disease (COPD) is largely underdiagnosed in patients with acute coronary syndrome (ACS) contributing to further affect clinical outcome. Our aim was to validate a screening procedure to identify, in ACS patients, those with negligible risk of undiagnosed COPD.From December 2014 to August 2015, 169 ACS patients with smoking history underwent screening procedure. Screening procedure combined peak expiratory flow rate (PEFR, defined as positive if80% of predicted) and respiratory health status questionnaire (RHSQ, defined as positive if19.5 points). The screening was considered negative if both tests provided negative results, positive if both were positive, uncertain in presence of discrepancy. Spirometry was planned after 2months to identify or not the presence of irreversible airflow obstruction (undiagnosed COPD). The primary endpoint was the negative predictive value of screening for undiagnosed COPD.Overall, 137 (81%) patients received spirometry (final study population). Screening was negative, uncertain and positive in 58 (42%), 46 (34%) and 33 (24%) patients, respectively. We found undiagnosed COPD in 39 (29%) patients. Only 3 patients with negative screening showed undiagnosed COPD. Negative screening showed the best ability to discriminate patients without COPD (negative predictive value 95%). Two-month health status in patients with undiagnosed COPD was significantly poor.Undiagnosed COPD is relatively frequent in ACS patients with smoking history and a simple screening procedure including PEFR and RHSQ can be administered before hospital discharge to discriminate those at negligible risk of undiagnosed COPD (ClinicalTrials.gov, NCT02324660).