Giuseppe Siniscalchi

Temporary caval stenting improves venous drainage during cardiopulmonary bypass

OBJECTIVES Assess the benefit of temporary caval stenting for remote venous drainage during cardiopulmonary bypass (CPB). METHODS Temporary caval stenting was realized in bovine experiments (65+/-6 kg) by the means of self-expanding (18F for insertion, 36F in situ) venous cannulas (Smartcanula LLC, Lausanne, Switzerland) with various lengths: 43 cm, 53 cm, 63 cm vs. a standard 28F wire armed cannula in trans-jugular fashion. Maximal blood flows were assessed for 20, 25 and 30 mmHg of driving pressure with a motorized table height adjustment system. In addition, the inferior caval diameters (just above its bifurcation) were measured in real time with intra-vascular ultrasound (IVUS). RESULTS Venous drainage (flow in l/min) at 20 mmHg, 25 mmHg, and 30 mmHg drainage load was 3.5+/-0.5, 3.7+/-0.7 and 4.0+/-0.6 for the 28F standard vs. 4.1+/-0.7, 4.0+/-1.3 and 3.9+/-1.1 for the 36F smart 43 cm, vs. 5.0+/-0.7, 5.3+/-1.3 and 5.4+/-1.4 for the 36F smart 53 cm, vs. 5.2+/-0.5*, 5.6+/-1.1* and 5.8+/-1.0* for the 36F smart 63 cm. The inferior vena caval diameters at 30 mmHg were 13.5+/-4.8 mm for 28F standard, 11.1+/-3.6 for 36F smart 43 cm, 11.3+/-3.2 for 36F 53 cm, and 17.0+/-0.1* for 36F 63 cm (*P<0.05 for 28F standard vs. 36F smart 63 cm long) CONCLUSIONS The 43 cm self-expanding 36F smartcanula outperforms the 28F standard wire armed cannula at low drainage pressures and without augmentation. Temporary caval stenting with long self-expanding venous cannulas provides even better drainage (+51%).

New Insights in the Diagnosis and Treatment of Heart Failure

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists.

Apical closure device for transapical valve procedures.

OBJECTIVES Transapical transcatheter valve procedures are performed through a left minithoracotomy and require apical sutures to seal the apical access site. The use of large-calibre devices compromises any attempt to fully perform the procedure with a thoracoscopic approach or percutaneously. We report our preliminary experience in animals with a new sutureless self-expandable apical occluder, engineered to perform transapical access site closure in a minimally invasive setting with large-size introducer sheaths. METHODS The apical occluder with extendable waist was implanted in six young pigs during an acute animal study. Under general anaesthesia, animals (mean weight: 62 ± 8 kg) received full heparinization (heparin: 100 UI/kg; activated clotting time above 250 s). Through a median sternotomy, a 21-Fr Certitude™ introducer sheath (outer diameter: 25 Fr) was placed over the wire into the cardiac apex. The delivery catheter carrying the constrained apical plug was inserted into the sheath and deployed under fluoroscopic control, whereas the Certitude™ was retrieved. After protamine infusion, we observed and recorded the 1-h bleeding with standard haemodynamic parameters. Animals were sacrificed, and hearts analysed. RESULTS Six apical closure devices were successfully introduced and deployed in six pig hearts through large-size apical sheaths at first attempt. In all animals, the plugs guaranteed immediate apical sealing and traces of blood were collected in the pericardium during the 1-h observational period (mean of 16 ± 3.4 ml of blood loss per animal). Haemodynamic parameters remained stable during the entire study period and no plug dislodgement was detected with normal systemic blood pressure (mean arterial mean blood pressure: 65 ± 7 mmHg). Post-mortem analysis confirmed the full deployment and good fixation of all plugs, without macroscopic damages to the surrounding myocardium. CONCLUSIONS This sutureless self-expandable apical occluder is a simple device capable of sealing large-size apical access sites (20-35 Fr) in an acute animal study. This approach is a step further towards less invasive transapical valve procedures in the clinical setting, and further animal tests will be performed to confirm the long-term efficacy and safety of this device.

Artificial muscle to wash blood out of fibrillating atrium: an alternative to lifelong anticoagulation.

The Atripump is a motorless, volume displacement pump based on artificial muscle technology that could reproduce the pump function of normal atrium. It could help prevent blood clots due to blood stagnation and eventually avoid anticoagulation therapy in atrial fibrillation (AF). An animal study has been designed to assess mechanical effects of this pump on fibrillating atrium. The Atripump is a dome shaped silicone coated nitinol actuator. A pacemaker like control unit drives the actuator. In five adult sheep, the right atrium (RA) was exposed and dome sutured onto the epicardium. Atrial fibrillation was induced using rapid epicardial pacing (600 beats/min). Ejection fraction of the RA was obtained with intracardiac ultrasound in baseline, AF and Atripump assisted AF conditions. The dome’s contraction rate was 60/min with power supply of 12V, 400 mA for 200 ms and ran for 2 hours in total. Mean temperature on the RA was 39 ± 1.5°C. Right atrium ejection fraction was 31% in baseline conditions, 5% and 20% in AF and assisted AF, respectively. In two animals a thrombus appeared in the right appendix and washed out once the pump was turned on. The Atripump washes blood out the RA acting as an anticoagulant device. Possible clinical implications in patients with chronic AF are prevention of embolism of cardiac origin and avoidance of hemorrhagic complication due to chronic anticoagulation.

Tropheryma whipplei bivalvular endocarditis and polyarthralgia: a case report

IntroductionTropheryma whipplei infection should be considered in patients with suspected infective endocarditis with negative blood cultures. The case (i) shows how previous symptoms can contribute to the diagnosis of this illness, and (ii) elucidates current recommended diagnostic and therapeutic approaches to Whipples disease.Case presentationA 71-year-old Swiss man with a past history of 2 years of diffuse arthralgia was admitted for a possible endocarditis with severe aortic and mitral regurgitation. Serial blood cultures were negative. Our patient underwent replacement of his aortic and mitral valve by biological prostheses. T. whipplei was documented by polymerase chain reactions on both removed valves and on stools, as well as by valve histology. A combination of hydroxychloroquine and doxycycline was initiated as lifetime treatment followed by the complete disappearance of his arthralgia.ConclusionsThis case report underlines the importance of considering T. whipplei as a possible causal etiology of blood culture-negative endocarditis. Lifelong antibiotic treatment should be considered for this pathogen (i) due to the significant rate of relapses, and (ii) to the risk of reinfection with another strain since these patients likely have some genetic predisposition.

Percutaneous increase of mitral leaflet coaptation length after mitral valve repair: results from a preclinical study†

OBJECTIVES The failure of mitral repairs can be the result of inadequate leaflet coaptation length (CL< 8 mm at the A2-P2 level). A new annuloplasty ring conceived by the authors enables post-surgical CL increase using percutaneous balloon catheter technology. We conducted preclinical studies to assess the in vivo feasibility of the procedure and the safety of the postimplant deformable mitral ring. METHODS The new annuloplasty ring allows the percutaneous and progressive displacement of each of the 3 anatomical regions of the posterior mitral annulus towards the anterior. Displacement is permanent and induced by an angioplasty balloon catheter inserted in a line connecting the ring to the subcutaneous tissue. Under general anaesthesia and cardiopulmonary bypass, healthy adult sheep had mitral annuloplasty. The device was implanted using the interrupted suture technique. The connection line exited the left atrium and reached the skin. Epicardial echocardiography allowed assessment of valve competence, leaflet CL, the mitral valve area and the mitral valve gradient. The mandrel was removed, and the dedicated catheter balloon was inserted into the connection line. The balloon was inflated in the P2 position under fluoroscopic control, and epicardial echocardiography was used to assess the functional parameters of the valve. One month later, the balloon was inserted again through the connection line; the P1 and P3 areas were deformed to increase CL. Valve parameters were measured again using transthoracic echocardiography. After 6 months, transthoracic echocardiography was used to assess the functional parameters of the valve. The sheep were sacrificed and autopsied. RESULTS Ten adult sheep survived the procedure. A 30-mm ring was implanted in all the sheep, and the 6-month follow-up was uneventful for all of them. The CL increased by 100% (4.2 ± 2 mm-8.5 ± 2 mm, P < 0.001); the transmitral gradient increased from 2 ± 0.5 mmHg to 4 ± 0.5 mmHg (P < 0.001) and the effective orifice area decreased from 4.5 ± 0.6 cm2 to 3.5 ± 0.6 cm2 (30% reduction, P < 0.001). CONCLUSIONS The device safely enabled a significant improvement of leaflet CL after mitral annuloplasty with an angioplasty-like technique, and the improvement was stable over time. The reshaping of the mitral annulus provided by this technology should benefit all patients having mitral repairs. The future of mitral regurgitation treatment is towards surgical correction followed by late, iterative, percutaneous adjustments of mitral leaflets coaptation.

Mastering Mitral Leaflets Coaptation after Valve Repair with Adjustable Mitral Annuloplasty Ring: proof of concept in mock loop study

This investigation sought to determine the feasibility of a novel mitral ring designed to reshape mitral annulus on beating heart, after surgery. The mitral ring is intended to improve mitral leaflets coaptation to correct residual and recurrent mitral regurgitations. It could also provide progressive correction of mitral regurgitation. The device was tested in ex vivo beating heart model. The novel mitral ring is selectively deformable in P1, P2, and P3 segments using a dedicated angioplasty-type balloon. The deformation should increase leaflets coaptation, reducing distance between the two leaflets. It was implanted using standard surgical techniques. The mock loop is based on passive beating heart. Mitral valve (MV) functioning was evaluated in terms of leaflets coaptation height at P2 level using epicardial echocardiography. The test has been completed on eight swine hearts. Ring size was 30 mm. The balloons were inserted in the connecting line. Each segment of the posterior annulus was independently activated over three progressive positions. Balloon inflation pressures were between 15 and 21 bar. Maximum coaptation height increase was 7 mm. Mean pressure gradient across the MV was 1.7 ± 0.3 mm Hg after complete activation of the device. The device allowed significant increase in coaptation height at P2 level after adjustments at P1, P2, and P3. Results were consistent and reproducible. This feasibility study demonstrates the possibility to reshape the mitral annulus on beating heart to precisely increase MV leaflets coaptation height.

A New Combined Technique Reducing the Risk of Paraplegia during Thoracoabdominal Aorta Replacement

Acute spinal cord ischemia during thoracoabdominal aorta replacement is a dreadful complication. Existing tools (motor evoked potential [MEP] and somatosensory evoked potential [SSEP]) do not allow differentiating between central and peripheral paraplegia. Therefore, the surgeon often performs unnecessary reimplantation of intercostal arteries: this is time consuming, and significantly increases bleeding complications. We present a simple technique combining MEP and peripheral compound muscle action potential induced by posterior tibialis nerve stimulation, enabling the surgeon to quickly discriminate between central and peripheral neurologic injury. The surgeon has one more tool to drive in real time the optimal surgical strategy. This strategy guides the decision as to which side branches ought to be reimplanted, thus minimizing the risk of paraplegia.

Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights

The aim of our current special issue was to present a series of original researches and reviews on recent advances in the diagnosis, medical therapy, and surgical approaches of heart failure. As reported in the introductive review of Agnetti et al., cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndromes are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The authors reported in this comprehensive review the evaluation of the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists. Among the studies included in this special issue, two of them investigated specific pathogenic aspects of heart failure. M. Kunin et al. studied the role of proinflammatory cytokines in congestive heart failure. In particular the authors evaluated the effect of peritoneal dialysis used in the long-term management of these patients on the peripheral-circulating levels of these cytokines. Interestingly, they found that peritoneal dialysis treatment caused a reduction in circulating inflammatory cytokines levels along with improvement in plasma markers of inflammation in patients with refractory chronic heart failure, concluding that this effect may be partly responsible for the efficacy of peritoneal dialysis for refractory heart failure. It is described that heart failure is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. To cast further light on this issue, A. Cabassi et al. investigated the relationship between plasma myeloperoxidase-related chlorinating activity, ceruloplasmin, and ferroxidase I and nitrosative stress and inflammatory, neurohormonal, and nutritional biomarkers in heart failure patients. This elegant study supported the conclusions that plasma myeloperoxidase chlorinated activity is increased in elderly patients who suffer from chronic heart failure and positively associated with ceruloplasmin and inflammatory, neurohormonal, and nitrosative parameters, suggesting a key role in heart failure progression. A major focus of studies on acute heart failure is the need for methods that allow the early detection of hemodynamic variables that can be a key prognostic role after cardiac surgery. F. Corradi et al. in their study investigated the Renal Doppler Resistive Index as a marker of oxygen supply and demand mismatch in 61 postoperative cardiac surgery patients. Interestingly, by multivariate analysis, Renal Doppler Resistive Index was significantly correlated with mixed-venous oxygen saturation, suggesting that, in mechanically ventilated patients after cardiac surgery, it could be used as a marker of early vascular response to tissue hypoxia. We must not forget that there are many patients suffering from heart failure secondary to extracardiac diseases. Among the causes of heart failure, an important place is held by cardiotoxicity due to antineoplastic treatments that has emerged as a clinically relevant problem as a consequence of the relevant improvement of survival after cancer. In the last decade recent advances have emerged in clinical and pathophysiological aspects of left ventricular dysfunction induced by the most widely used anticancer drugs. M. Molinaro et al., in their comprehensive review entitled “Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs,” have particularly examined the role of early, sensitive markers of cardiac dysfunction, in order to predict this form of cardiomyopathy before left ventricular ejection fraction is reduced. It seems actually that this is increasingly important issue, along with the evaluation of novel therapeutic and cardioprotective strategies, to protect cardiooncologic patients from the development of congestive heart failure. As reported by A. Adegunsoye et al., there are also a consistent number of patients who die due to right heart failure and pulmonary hypertension secondary to fibrotic lung diseases. Significant factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. The authors have reported an exhaustive review of novel therapeutic strategies for reducing right heart failure associated mortality in fibrotic lung diseases, because only “an early, effective and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life.” Another major focus of studies on acute heart failure is related to the evaluation of new surgical alternatives to transplantation or new systems or new materials available for future cardiac assist devices. In this special issue the review of J. Anand et al. explores the evolution of mechanical circulatory support and its potential for providing long-term therapy, which may address the limitations of cardiac transplantation. The innovation progresses have led to a solution of current challenges involving device complications. Moreover outcomes continue to improve and further data from both small and large registries help to advance evidence-based practices: thus patients in the most advanced stages of heart failure appear to have more hope than ever before. On the other hand the high costs, expanding indications, and rapidly increasing number of devices implanted will ultimately require important decisions to be made on the part of society, clinicians, and administrative agencies in order to establish the potential amount of economic resources to spend on this expensive, yet effective, therapy. Patient selection will remain paramount, although a very large population of patients will have the potential to benefit. In particular, K. Unthan et al. reported a study on the design and evaluation of a fully implantable control unit for blood pumps. It is well known that pneumatic devices sufficiently supply the patients with blood flow, although the patients quality of life is limited by the percutaneous pressure lines and the size of the external control unit. General requirements for any implantable control unit are defined from a technical and medical point of view: need for a Transcutaneous Energy Transmission, autonomous operation, safety, geometry, and efficiency. The authors described the development of the control unit of the ReinHeart, a fully implantable Total Artificial Heart that, in validation tests, is demonstrated to be a stable operation with a promising good efficiency. Finally P. Morillas-Sendin et al. assessed the effect of sevoflurane and propofol on organ blood flow in a porcine model with a left ventricular assist device. The authors demonstrated that, compared with propofol, sevoflurane increases blood flow in the brain, liver, and heart after implantation of a left ventricular assist device under conditions of partial support, giving interesting indications for the intensive pharmacological care of these high-risk patients. The modern approach to the diagnosis and treatment of heart failure is multidisciplinary and should be based on a close collaboration among researchers, clinicians, and cardiac surgeons particularly given that mandatory multiorgan attention is required in these high-risk patients. Future therapies for heart failure could include ventricular assist devices implantation or ventricular restoration techniques with the aim to obtain a reverse, positive remodeling in the unloaded heart. With an expanding “toolbox” of comprehensive basic, medical, surgical, and technological approaches, it is expected that these novel findings will soon be translated to the clinical practice. In fact, new therapeutic strategies are needed by the millions of patients suffering from heart failure. We hope that this special issue will help readers become familiarized with recent progress regarding the diagnosis and treatment of heart failure.

Severe atherosclerotic aortoiliac occlusive disease in a young HIV-infected patient

A 39-year-old white man with CDC stage C3 HIV infection who had been diagnosed at 23 years of age presented with complaints of progressive lower limb pain, which had been aff ecting him during periods of exertion for 6 months. His lowest CD4 T-lymphocyte count had been 50 cells per μL. After 11 years of various combinations of antiretroviral drugs, the count had stabilised at 150 cells per μL despite persistent undetectable viraemia. The limb pain appeared after a 100 m walk and disappeared after a few minutes at rest. His cardiovascular risk factors were smoking and modest hypercholesterolaemia. Femoral, popliteal, and ankle pulses were palpable on both legs. There was an abdominal bruit. Ankle arterial pressure was measured with a Doppler probe: ankle-brachial pressure index was 0·98 right and 0·84 left at rest (normal more than 0·90), and fell deeply to 0·41 right, 0·30 left after a 100 m walk on the treadmill, which reproduced the claudication. A duplex ultrasound of the lower limb arteries identifi ed an 80% stenosis of the distal abdominal aorta resulting from a large atherosclerotic plaque. This fi nding was confi rmed by CT scan (fi gure, A; arrow indicates plaque), which showed extension of the plaque to the proximal lumen of both common iliac arteries. A surgical endarteriectomy and enlargement of the aortoiliac junction was done with resection of a large, partly calcifi ed and thrombosed plaque of atheroma (fi gure, B and C). 1 month later the patient completed 500 m on the treadmill (12% uphill, 3·5 km/h) without any pain or decrease of ankle-brachial pressure index. Lifestyle modifi cation and drug intervention were initiated to decrease his risk of cardiovascular event. Now, almost 1 year after surgery, the patient enjoys walking and remains free of any claudication. Coronary, cerebral, and peripheral arterial diseases are frequently seen in HIV-infected patients, since potent antiviral treatments have off ered prolonged survival. Premature atherosclerosis can result from long exposure to drug-induced hyperlipidaemia and hyperglycaemia, and also from chronic infl ammation, magnifying a classic cardiovascular risk factor such as heavy smoking.