Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous-flow left ventricular assist device.

AIMS: To correlate the dynamics of platelet activation with the development of thromboembolic events in patients with continuous-flow left ventricular assist device (cf-LVAD). METHODS AND RESULTS: The platelet activity state (PAS) assay was utilized to evaluate platelet activation in 68 cf-LVAD patients implanted with the HeartMate II (n = 15, 22%), HeartMate 3 (n = 15, 22%), or HeartWare HVAD (n = 38, 56%). PAS was measured preoperatively, early post-implant, and at long-term follow-up (1, 3, 6, 12, 18, and 24 months post-implant). PAS was also measured at the occurrence of adverse events in patients who developed thrombotic complications. Data on patient demographics, medical history, antithrombotic therapy, and coagulation parameters were also analysed. Over a median follow-up of 602 (234-942) days, PAS values did not increase over time in the overall population (P = 0.15). However, PAS measured at event was 15-fold higher in the six patients (9%) who suffered pump thrombosis (n = 2) or ischaemic stroke (n = 4) vs. the rest of the population [6.67% (5.59%-11.98%) vs. 0.45% (0.33%-0.75%); P = 0.012], despite comparable coagulation profile. Pre-implant PAS values were 4.5-fold higher in these patients [1.90% (1.24%-3.17%) vs. 0.42% (0.32%-0.72%); P = 0.006]. Neither preoperative variables nor the type of the pump or the antiplatelet strategy were associated with a higher risk of complications. CONCLUSIONS: Thrombotic events are associated with altered PAS values. Moreover, baseline elevated PAS values in patients who developed thrombotic events suggest patient-specific tendency to post-implant thromboembolic complications. Prospectively, systematic monitoring of PAS might guide the development of refined patient-tailored antithrombotic strategies and the technological improvement of LVAD design.

Heart rate as a prognostic marker and therapeutic target in acute and chronic heart failure.

Since increased heart rate (HR) is associated with higher mortality in several cardiac disorders, HR is considered not only a physiological indicator but also a prognostic and biological marker. In heart failure (HF), it represents a therapeutic target in chronic phase. The use or up-titration of beta-blockers, a milestone in HF with reduced left ventricular ejection fraction (LVEF) treatment, is at times limited by patients' hemodynamic profile or intolerance. Ivabradine, a HR-lowering drug inhibiting the f-current in pacemaker cells, has been shown to improve outcome in patients with chronic HF, in sinus rhythm with increased HR beyond beta-blocker therapy. The rationale for this review is to update the role of HR as a prognostic biomarker and a potential therapeutic target in other scenarios than chronic HF; namely, in patients with coexisting atrial fibrillation (AF), in HF with preserved LVEF (HFpEF), in acute HF, and in patients discharged after an episode of acute HF. Preliminary studies and case reports that evaluated the use of ivabradine in the setting of acute HF will be summarized. Recent results of HR reduction in the setting of HFpEF with ivabradine will be presented. Finally, data from large registries and trials that evaluated the prognostic impact of HR in patients with acute HF and sinus rhythm or AF will be reviewed, showing that only patients in sinus rhythm may benefit from HR reduction.

Echocardiographic guidance and monitoring of left atrial appendage closure with AtriClip during open-chest cardiac surgery.

Left atrial appendage (LAA) closure prevents thromboembolic risk and avoids lifelong anticoagulation due to atrial fibrillation (AF). Nowadays, AtriClip, a modern epicardial device approved in June 2010, allows external and safe closure of LAA in patients undergoing cardiac surgery during other open-chest cardiac surgical procedures. Such a surgical approach and its epicardial deployment differentiates LAA closure with AtriClip from percutaneous closure techniques such as Watchman (Boston Scientific, Marlborough, MA, USA), Lariat (SentreHEART Inc., Redwood City, CA, USA), and Amplatzer Amulet (St. Jude Medical, St. Paul, MN, USA) device procedures. AtriClip positioning must consider perioperative transesophageal echocardiography (TEE) to confirm LAA anatomical features, to explore the links with neighboring structures, and finally to assess its successful closure. We report a sequence of images to document the role of intraoperative TEE during an elective aortic valve replacement and LAA external closure with AtriClip.

Concomitant implantation of Impella® on top of veno-arterial extracorporeal membrane oxygenation may improve survival of patients with cardiogenic shock.

AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support stabilizes patients with cardiogenic shock. Despite improved oxygenation and peripheral circulation, LV unloading may be impeded due to the increased afterload, resulting in a failing static left ventricle and in high mortality. METHODS AND RESULTS: We describe for the first time a large series of patients treated with the combination of VA-ECMO and Impella® compared with patients with VA-ECMO only. We retrospectively collected data on patients from two tertiary critical care referral centres. We enrolled 157 patients treated with VA-ECMO from January 2013 to April 2015: 123 received VA-ECMO support and 34 had concomitant treatment with VA-ECMO and Impella. A propensity-matching analysis was performed in a 2:1 ratio, resulting in 42 patients undergoing VA-ECMO alone (control group) compared with 21 patients treated with VA-ECMO and Impella. Patients in the VA-ECMO and Impella group had a significantly lower hospital mortality (47% vs. 80%, P < 0.001) and a higher rate of successful bridging to either recovery or further therapy (68% vs. 28%, P < 0.001) compared with VA-ECMO patients. A higher need for continuous veno-venous haemofiltration (48% vs. 19%, P = 0.02) and increased haemolysis (76% vs. 33%, P = 0.004) were reported in the study group due to higher survival. There was no difference in major bleeding rates between the two groups (VA-ECMO and Impella 38% vs. VA-ECMO 29%, P = 0.6). CONCLUSIONS: Concomitant treatment with VA-ECMO and Impella may improve outcome in patients with cardiogenic shock compared with VA-ECMO only. Nevertheless, randomized studies are needed to validate these promising results further.

Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives.

Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease-specific pharmacological therapy. For over 50 years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time-honoured therapies available for HCM, in a practical perspective reflecting real-world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end-stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre-clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed.

The contemporary role of Impella in a comprehensive mechanical circulatory support program: a single institutional experience.

BACKGROUND: The treatment of cardiogenic shock with percutaneous mechanical circulatory support (MCS) is attractive: however, at present it is not clear which is the best strategy, as no survival benefit has been demonstrated for any device as single therapy. Aim of this study is to describe the role of percutaneous Impella in a comprehensive MCS program. METHODS: Observational study on 22 patients supported with the Impella device in our hospital from May 2013 to June 2014. RESULTS: Four patients (18 %) were treated with Impella alone, 8 patients (36 %) were treated with Impella and IABP, 6 patients (27 %) with Impella and VA ECMO, and 4 patients (18 %) with Impella, IABP and VA ECMO. The cause of cardiogenic shock was myocardial infarction (CSMI) in 9 patients (41 %), postcardiotomic cardiogenic shock in 5 (23 %), and a miscellaneous of other causes in the remaining 8 (36 %). Eight Impella devices (36 %) were placed under transesophageal echocardiographic guidance, while 14 (64 %) under fluoroscopy. The device was removed with manual compression at bedside and no vascular complications were observed. Duration of Impella support was 107 (54-141) hours and duration of ventilation was 48 (14-92) hours. Hemolysis occurred in 6 patients (27 %), while major bleeding in 4 patients (18 %). Survival was 73 %: 13 patients (58 %) showed recovery of cardiac function; 1 patient (5 %) was bridged to left ventricular assist device (LVAD) implantation, 1 patient (5 %) to heart transplantation (HTx) and 1 patient (5 %) received a BiVAD and was eventually bridged to HTx. CONCLUSIONS: Our data suggest that a multi-device approach, encompassing active LV support with Impella, is safe and can significantly improve survival in patients with cardiogenic shock.

Drug-Coated Balloons Versus Second-Generation Drug-Eluting Stents for the Management of Recurrent Multimetal-Layered In-Stent Restenosis.

OBJECTIVES: This study aimed to investigate the clinical outcomes of patients presenting with recurrent drug-eluting stent (DES) in-stent restenosis (ISR) treated with a second-generation DES or with a drug-coated balloon (DCB). BACKGROUND: To date, there are no reports of DCB treatment and limited data with regard to the efficacy of further DES implantation for recurrent ISR. METHODS: Between January 2008 and December 2013, 171 lesions were assessed for eligibility (82 lesions in the second-generation DES group and 89 lesions in the DCB group). RESULTS: Acute gain was greater in the second-generation DES group (second-generation DES, 2.09 ± 0.53 mm vs. DCBs, 1.60 ± 0.62 mm, p < 0.001). The rates of major adverse cardiac events were comparable (at 1 year, DES 14.0% vs. DCBs 12.3%; at 2 years, DES 28.8% vs. DCBs 43.5%, p = 0.21). Major adverse cardiac event rates were mainly driven by target lesion revascularization (at 1 year, DES 12.5% vs. DCBs 10.9%; at 2 years, DES 27.7% vs. DCBs 38.3%; p = 0.40). Definite scaffold thrombosis occurred in 2 patients (1 patient in each group). Multivariable analysis revealed ISR recurrence within 1 year (hazard ratio: 2.43, 95% confidence interval: 1.14 to 5.18, p = 0.02) and lesion length (per 10-mm increase) (hazard ratio: 1.15, 95% confidence interval: 1.00 to 1.32, p = 0.049) to be independent predictors of TLR. CONCLUSIONS: The results after both treatments were equivalent. ISR recurrence within 1 year of the first reintervention and lesion length were independent predictors of future target lesion revascularization. Larger studies are required to confirm the late (>1 year) differences with regard to clinical outcomes.

Current indications for heart transplantation and left ventricular assist device: a practical point of view.

Heart transplantation (HTx) is considered the "gold standard" therapy of refractory heart failure (HF), but it is accessible only to few patients because of the paucity of suitable heart donors. On the other hand, left ventricular assist devices (LVADs) have proven to be effective in improving survival and quality of life in patients with refractory HF. The challenge encountered by multidisciplinary teams in dealing with advanced HF lies in identifying patients who could benefit more from HTx as compared to LVAD implantation and the appropriate timing. The decision-making is based on clinical parameters, imaging-based data and risk scores. Current outcome of HF patients supported by LVAD (2-year survival around 70%) is rapidly improving and leads the way to a new therapeutic strategy. Patients who have a low likelihood to gain access to the heart graft pool could benefit more from LVAD implantation (defined as bridge to transplantation indication) than from remaining on HTx waiting list with the likely risk of clinical deterioration or removal from the list because patients are no longer suitable for transplantation. LVAD has also demonstrated to be effective in patients who are not considered eligible candidates for HTx with a destination therapy indication. HTx should be reserved to those patients for whom the maximum clinical benefit can be expected, such as young patients with no comorbidities. Here we discuss the current listing criteria for HTx and indications to implant of LVAD for patients with refractory acute and chronic HF based on the guidelines and the practical experience of our center.

[Cardiac involvement by non-Hodgkin's lymphoma in an HIV-positive patient with hypertrophic obstructive cardiomyopathy]. / Localizzazione cardiaca di linfoma non-Hodgkin in soggetto HIV positivo affetto da cardiomiopatia ipertrofica ostruttiva.

Cardiac onset of a diffuse large B-cell lymphoma (DLBCL) in a HIV+ patient with hypertrophic obstructive cardiomyopathy. The sequence of diagnosis, therapeutical planning and final outcome underlines the importance of an early diagnosis that cannot be conceived without an increased attention in this clinical setting (aspecific symptoms in an HIV positive subject) by the General Practitioner.