Mechanical assist devices for acute cardiogenic shock.

BACKGROUND: Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors, inotropic support and intra-aortic balloon pump, mortality approaches 100%. Mechanical assist devices provide mechanical circulatory support (MCS) which has the ability to maintain vital organ perfusion, to unload the failing ventricle thus reduce intracardiac filling pressures which reduces pulmonary congestion, myocardial wall stress and myocardial oxygen consumption. This has been hypothesised to allow time for myocardial recovery (bridge to recovery) or allow time to come to a decision as to whether the person is a candidate for a longer-term ventricular assist device (VAD) either as a bridge to heart transplantation or as a destination therapy with a long-term VAD. OBJECTIVES: To assess whether mechanical assist devices improve survival in people with acute cardiogenic shock. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection in November 2019. In addition, we searched three trials registers in August 2019. We scanned reference lists and contacted experts in the field to obtain further information. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials on people with acute CS comparing mechanical assist devices with best current intensive care management, including intra-aortic balloon pump and inotropic support. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the published protocol. Primary outcomes were survival to discharge, 30 days, 1 year and secondary outcomes included, quality of life, major adverse cardiovascular events (30 days/end of follow-up), dialysis-dependent (30 days/end of follow-up), length of hospital stay and length of intensive care unit stay and major adverse events. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes Summary statistics for the primary endpoints were risk ratios (RR), hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: The search identified five studies from 4534 original citations reviewed. Two studies included acute CS of all causes randomised to treatment using TandemHeart percutaneous VAD and three studies included people with CS secondary to acute myocardial infarction who were randomised to Impella CP or best medical management. Meta-analysis was performed only to assess the 30-day survival as there were insufficient data to perform any further meta-analyses. The results from the five studies with 162 participants showed mechanical assist devices may have little or no effect on 30-day survival (RR of 1.01 95% CI 0.76 to 1.35) but the evidence is very uncertain. Complications such as sepsis, thromboembolic phenomena, bleeding and major adverse cardiovascular events were not infrequent in both the MAD and control group across the studies, but these could not be pooled due to inconsistencies in adverse event definitions and reporting. We identified four randomised control trials assessing mechanical assist devices in acute CS that are currently ongoing. AUTHORS' CONCLUSIONS: There is no evidence from this review of a benefit from MCS in improving survival for people with acute CS. Further use of the technology, risk stratification and optimising the use protocols have been highlighted as potential reasons for lack of benefit and are being addressed in the current ongoing clinical trials.

Can we remove scar and fibrosis from adult human myocardium?

The pathological processes leading to heart failure are characterized by the formation of fibrosis and scar, yet the dynamics of scar production and removal are incompletely understood. Spontaneous disappearance of myocardial collagen is reported in infancy but doubted in adulthood where scar volume constitutes a better prognostic indicator than the conventional parameters of ventricular function. Whilst certain drugs are known to attenuate myocardial fibrosis evidence is emerging that stem cell therapy also has the potential to reduce scar size and improve myocardial viability. Both animal studies and clinical trials support the concept that, as in infancy, cellular processes can be triggered to remove collagen and regenerate injured myocardium. The molecular mechanisms likely involve anti-fibrotic cytokines growth factors and matrix-metalloproteinases. Autologous cardiac, bone-marrow and adipose tissue derived stem cells have each shown efficacy. Specific immune privileged mesenchymal stem cells and genetically modified immunomodulatory progenitor cells may in turn provide an allogenic source for the paracrine effects. Thus autologous and allogenic cells both have the potential through paracrine action to reduce scar volume, boost angiogenesis and improve ventricular morphology. The potential benefit of myocardial cell therapy for routine treatment of heart failure is an area that requires further study.

The CentriMag centrifugal blood pump as a benchmark for in vitro testing of hemocompatibility in implantable ventricular assist devices.

Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P < 10(-5) ), and the level of high molecular weight of vWF multimers was significantly reduced in the CentriMag (P < 10(-5) ) all compared with the static treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle formation, and cleavage of vWF multimers, these results show that the CentriMag is a hemocompatible pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps.

Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction.

BACKGROUND: Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function. METHODS: Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively. RESULTS: AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (-16.4 ± 2.7% vs. controls -21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (-19.4 ± 2.5%) improved significantly. CONCLUSIONS: Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand-supply balance to preserve myocardial energetics and LV function are promising future therapies.

Evolution of a circulatory support system with full implantability: personal perspectives on a long journey.

Implantable mechanical circulatory support systems have evolved dramatically over the last 50 years. The objective has been to replace or support the failing left ventricle with a device that pumps six litres of blood each minute, a massive 8,640 litres per day. Noisy cumbersome pulsatile devices have been replaced by smaller silent rotary blood pumps that are much more patient friendly. Nonetheless, the tethering to external components, together with the risks of power line infection, pump thrombosis and stroke, must be addressed before widespread acceptance. Infection predisposes to thromboembolism, so elimination of the percutaneous electric cable has the capacity to transform outcomes, reduce costs and improve quality of life. Developed in the UK, the Calon miniVAD is powered by an innovative coplanar energy transfer system. As such, we consider it can achieve those ambitious objectives.

Transcriptomal Insights of Heart Failure from Normality to Recovery.

Current management of heart failure (HF) is centred on modulating the progression of symptoms and severity of left ventricular dysfunction. However, specific understandings of genetic and molecular targets are needed for more precise treatments. To attain a clearer picture of this, we studied transcriptome changes in a chronic progressive HF model. Fifteen sheep (Ovis aries) underwent supracoronary aortic banding using an inflatable cuff. Controlled and progressive induction of pressure overload in the LV was monitored by echocardiography. Endomyocardial biopsies were collected throughout the development of LV failure (LVF) and during the stage of recovery. RNA-seq data were analysed using the PANTHER database, Metascape, and DisGeNET to annotate the gene expression for functional ontologies. Echocardiography revealed distinct clinical differences between the progressive stages of hypertrophy, dilatation, and failure. A unique set of transcript expressions in each stage was identified, despite an overlap of gene expression. The removal of pressure overload allowed the LV to recover functionally. Compared to the control stage, there were a total of 256 genes significantly changed in their expression in failure, 210 genes in hypertrophy, and 73 genes in dilatation. Gene expression in the recovery stage was comparable with the control stage with a well-noted improvement in LV function. RNA-seq revealed the expression of genes in each stage that are not reported in cardiovascular pathology. We identified genes that may be potentially involved in the aetiology of progressive stages of HF, and that may provide future targets for its management.

Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion.

We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

Mitral stenosis.

Mitral stenosis is a common disease that causes substantial morbidity worldwide. The disease is most prevalent in developing countries, but is increasingly being identified in an atypical form in developed countries. All treatments that increase valve area improve morbidity. Mortality improves with surgery; the benefit of percutaneous balloon valvuloplasty to mortality might be similar to that of surgery but needs further study. Percutaneous balloon valvuloplasty is the treatment of choice for patients in whom treatment is indicated, except for those with suboptimum valve morphology, and even these patients are sometimes treated with this procedure if surgery is not feasible or if surgical risk is prohibitive. We review the pathology, diagnosis, and treatment options for patients with mitral stenosis.

Endovascular stent placement is an acceptable alternative to reoperation in selected infants with residual or recurrent aortic arch obstruction.

OBJECTIVE: To describe endovascular stent placement in infants as a technically feasible option in circumstances where surgery is considered less favorable. BACKGROUND: Endovascular stent placement has become established as a first line therapy for native coarctation of the aorta or recoarctation in older children where stents capable of expansion to adult size can be placed safely. Surgery remains the therapy of choice in infants and young children. The management of aortic arch obstruction in infants is, however, frequently complicated by complex anatomy or clinical condition that may make surgery or further surgery an unattractive option. There is little reported data and the implications thereof of transcatheter stent placement in aortic arch obstruction in infants. METHODS: Between August 2004 and November 2009, 11 patients had aortic arch obstruction treated with endovascular stent placement. The median age and weight at first stent placement was 46 days (range 3-399 days) and 4 kg (range 1.4-8 kg), respectively. In 10 patients, surgical intervention preceded transcatheter stent placement. Four had complex aortic arch obstruction and seven had recoarctation. RESULTS: Reduction in peak systolic gradient to <10 mm Hg was achieved in seven of 10 patients with an improvement in aortic artery diameter to >90% of adjacent aorta in all. The diameter of the arch obstruction increased from a median of 1.60 to 4.90 mm (P = 0.001) and the peak systolic gradient from 45 mm Hg to 8 mm Hg (P < 0.0001). Adverse events occurred in two patients one who required further surgical revision and a second who required placement of a second stent. The median follow up was 3.60 years (range 0.4-5.5 years) with two patients having died at 1.34 and 1.42 years poststent placement. Of the nine patients alive, six have since undergone further angioplasty at a median time interval of 0.77 years (range 0.17-2.76 years). Long-term complications occurred in none. CONCLUSIONS: Endovascular stent placement in infants is technically feasible with good results achievable even in small babies. It should be considered as a therapeutic option in complex cases when surgical alternatives are less favorable.

Minimal extracorporeal circulation circuit standby for "off-pump" left ventricular assist device implantation.

We propose, as an addition to the off-pump technique for implantation of an axial flow left ventricular assist device, the use of a minimal extracorporeal circuit for circulatory support, in the setting of hemodynamic instability during implantation. Thus, the use of conventional cardiopulmonary bypass could be avoided. This set-up provides simplicity and effectiveness and enhanced safety of the off-pump implantation while it may offer adequate circulatory support if required.

Consensus statement: minimal criteria for reporting the systemic inflammatory response to cardiopulmonary bypass.

The lack of established cause and effect between putative mediators of inflammation and adverse clinical outcomes has been responsible for many failed anti-inflammatory interventions in cardiopulmonary bypass (CPB). Candidate interventions that impress in preclinical trials by suppressing a given inflammation marker might fail at the clinical trial stage because the marker of interest is not linked causally to an adverse outcome. Alternatively, there exist examples in which pharmaceutical agents or other interventions improve clinical outcomes but for which we are uncertain of any antiinflammatory mechanism. The Outcomes consensus panel made 3 recommendations in 2009 for the conduct of clinical trials focused on the systemic inflammatory response. This panel was tasked with updating, as well as simplifying, a previous consensus statement. The present recommendations for investigators are the following: (1) Measure at least 1 inflammation marker, defined in broad terms; (2) measure at least 1clinical end point, drawn from a list of practical yet clinically meaningful end points suggested by the consensus panel; and(3) report a core set of CPB and perfusion criteria that maybe linked to outcomes. Our collective belief is that adhering to these simple consensus recommendations will help define the influence of CPB practice on the systemic inflammatory response, advance our understanding of causal inflammatory mechanisms, and standardize the reporting of research findings in the peer-reviewed literature.

Ventricular septal rupture following abciximab infusion.

Ventricular septal rupture is a rare complication of myocardial infarction. Despite a significant reduction in its incidence with reperfusion therapy, thrombolysis has been implicated in the pathogenesis of septal rupture. There is little information regarding the impact of glycoprotein IIb-IIIa receptor blockers on ventricular septal rupture. We report a case of rupture of the ventricular septum occurring after treatment with the glycoprotein IIb-IIIa receptor blocker abciximab, in the absence of thrombolysis.

Lifetime circulatory support must not be restricted to transplant centers.

Heart failure that does not respond to maximum medical management is a frightening and debilitating condition. The patients have poor quality of life and become progressively more dependent on hospital admissions for escalating medical therapy. Long-term circulatory support can provide symptomatic relief and improved survival for those who do not have access to cardiac transplantation. User-friendly blood pumps with proven durability already exist. Rotary blood pumps must be made available in centers other than those involved in transplantation. The mystique must be removed from this relatively simple intervention.

Surgery for heart failure: now something for everyone?

For the past 50 years cardiac surgery has been in a continuous state of flux. Non-transplant heart failure surgery is an expanding field at a time when medical treatment and cardiac resynchronization therapy have recognized limits. Although donor hearts can be supplied to only a tiny minority of patients who have heart failure, other surgical options may soon provide symptomatic relief for the majority. Left ventricular restoration surgery is predicated on the well-defined relationship between cardiac shape, volume, and function. The recent remarkable developments in blood pump bioengineering provide an alternative approach and a platform on which to base genetic or stem cell therapies.

Maximizing survival potential in very high risk cardiac surgery.

The mean age and risk profile of patients referred for cardiac surgery is constantly increasing. Surgeons are now inclined to accept high-risk patients because interventional cardiology provides less invasive alternatives for an overlapping patient cohort. As risk profile increases so does hospital mortality. Patients who are difficult to wean from cardiopulmonary bypass and those who subsequently deteriorate into a low cardiac output state have mortality rates between 50% and 80%. In established cardiogenic shock, conventional treatment with inotropes, the intra-aortic balloon pump, or temporary circulatory support devices has not substantially improved survival. In the absence of the transplant option, more innovative circulatory support strategies are required to improve survival in the postcardiotomy setting.