Management of ganciclovir resistance cytomegalovirus infection with CMV hyperimmune globulin and leflunomide in seven cardiothoracic transplant recipients and literature review.

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single-center experience over 6 years (2011-2017).

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single-center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a "rescue therapy" in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV-related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.

Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

AIMS: Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. METHODS AND RESULTS: TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n = 443) had a mean age of 68.8 ± 11.2 years, 77% male (usual care cohort: n = 315, mean age of 66.2 ± 14.5 years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30 day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10 min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P = 0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P = 0.077). CONCLUSIONS: These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.

Axillary intra-aortic balloon pump, biventricular assist device implantation and subsequent orthotopic heart transplantation in a patient with sickle cell trait.

A 38-year-old male with sickle cell trait and acute refractory heart failure received an axillary intra-aortic balloon pump and short-term biventricular assist device. He underwent orthotopic heart transplantation 45 days later, which was complicated by major bleeding necessitating significant intra-operative transfusion. Support with veno-arterial extracorporeal membrane oxygenation was provided and successfully weaned five days later. He made a full recovery and remains alive and well 34 months after discharge. We hypothesize that the protective peri-operative measures undertaken, including normothermia during surgery and post-operative haemodynamic stability due to the use of mechanical circulatory support, conveyed a degree of protection against complications associated with sickle cell dysfunction and contributed to the successful outcome.

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices.

Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients.

Invasive Haemodynamic Assessment Before and After Left Ventricular Assist Device Implantation: A Guide to Current Practice.

Mechanical circulatory support for the management of advanced heart failure is a rapidly evolving field. The number of durable long-term left ventricular assist device (LVAD) implantations increases each year, either as a bridge to heart transplantation or as a stand-alone 'destination therapy' to improve quantity and quality of life for people with end-stage heart failure. Advances in cardiac imaging and non-invasive assessment of cardiac function have resulted in a diminished role for right heart catheterisation (RHC) in general cardiology practice; however, it remains an essential tool in the evaluation of potential LVAD recipients, and in their long-term management. In this review, the authors discuss practical aspects of performing RHC and potential complications. They describe the haemodynamic markers associated with a poor prognosis in patients with left ventricular systolic dysfunction and evaluate the measures of right ventricular (RV) function that predict risk of RV failure following LVAD implantation. They also discuss the value of RHC in the perioperative period; when monitoring for longer term complications; and in the assessment of potential left ventricular recovery.

Financial implications of using extracorporeal membrane oxygenation following heart transplantation.

OBJECTIVES: Primary graft dysfunction after heart transplant is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) can be used to wean patients from cardiopulmonary bypass. This study retrospectively reviews a single-centre experience of post-transplant ECMO in regard to outcomes and associated costs. METHODS: Between May 2006 and May 2019, a total of 267 adult heart transplants were performed. We compared donor and recipient variables, ECMO duration and the incidence of renal failure, bleeding, infection and cost analysis between ECMO and non-ECMO groups. RESULTS: ECMO support was required postoperatively to manage primary graft dysfunction in 72 (27%) patients. The mean duration of ECMO support was 6 ± 3.2 days. Mean ischaemic times were similar between the groups. There was a significantly higher proportion of ventricular assist device explant to transplant in the ECMO group versus non-ECMO (38.2% vs 14.1%; P < 0.0001). ECMO patients had a longer duration of stay in the intensive care unit (P < 0.0001) and total hospital stay (P < 0.0001). Greater mortality was observed in the ECMO group (P < 0.0001). The median cost of providing ECMO was £18 000 [interquartile range (IQR): £12 750-£24 000] per patient with an additional median £35 225 (IQR: £21 487.25-£51 780.75) for ITU stay whilst on ECMO. The total median cost per patient inclusive of hospital stay, ECMO and dialysis costs was £65 737.50 (IQR: £52 566.50-£95 221.75) in the non-ECMO group compared to £145 415.71 (IQR: £102 523.21-£200 618.96) per patient in the ECMO group (P < 0.0001). CONCLUSIONS: Patients with primary graft dysfunction following heart transplantation who require ECMO are frequently bridged to a recovery; however, the medium and longer-term survival for these patients is poorer than for patients who do not require ECMO.

The introduction of a super-urgent heart allocation scheme in the UK: A 2-year review.

BACKGROUND: In response to a growing number of patients on the UK urgent heart transplant waiting list, the UK donor heart allocation scheme was revised in October 2016 with the introduction of a new super-urgent category. Patients with temporary mechanical circulatory support (tMCS) became eligible for super-urgent registration. The aim of this study was to compare activity, indications, and outcomes before and after the change. METHODS: Data on adult (aged ≥16 years) heart transplant registrations and recipients in the 2 years before (Era 1: July 1, 2014-June 30, 2016) and after (Era 2: January 2017-December 2018) the introduction of the new scheme were extracted from the UK Transplant Registry and analyzed using competing risks analysis, Kaplan-Meier analysis, and Cox proportional-hazards regression. RESULTS: There were 525 waiting-list registrations in Era 1 and 594 in Era 2, including 14% super-urgent registrations, with 90% having some form of tMCS. Median waiting time to transplant was 41 days for all urgent registrations in Era 1 compared with 17 days for super-urgent registrations and 71 days for urgent registrations in Era 2. Numbers of non-urgent transplants were not affected. Deaths on the waiting list significantly decreased from 5% to 2% at 6 months between Era 1 and Era 2 (adjusted hazard ratio = 0.29, 95% CI = 0.13-0.62). In addition, total number of patients with tMCS were not different between both eras, suggesting no significant change in this area of clinical decision making. Post-transplant survival at 1 year for super-urgent recipients was not significantly different from post-transplant survival at 1 year for other categories. CONCLUSIONS: The Introduction of a super-urgent heart allocation scheme in the UK reduces waiting time to transplant for the sickest patients, with comparable post-transplant survival while reducing deaths on the waiting list.

Establishing a heart transplant programme using donation after circulatory-determined death donors: a United Kingdom based single-centre experience.

OBJECTIVES: Demand for heart transplant donors worldwide continues to outstrip supply. Transplanting hearts following donation after circulatory-determined death (DCD) is increasingly recognized as a safe and effective alternative. As the fourth centre worldwide to have established such a programme, our goal was to present our initial experience. METHODS: This was a single-centre retrospective observational study. All DCD hearts were retrieved using direct procurement and perfusion. Continuous normothermic perfusion of the procured heart was then established on the TransMedics® Organ Care System. The primary outcome of this study was the 30-day survival rate. RESULTS: Between May 2017 and December 2018, 8 DCD hearts were procured and 7 were subsequently implanted, including in 2 patients who had left ventricular assist devices explanted. During the same time period, 30 patients received donation after brainstem death heart transplants. Therefore, the DCD heart transplant programme led to a 23% increase in transplant activity. The median donation warm ischaemic time was 34 min [interquartile range (IQR) 31-39 min]. The median functional warm ischaemic time was 28 min (IQR 25-30 min). The median time spent by the organ on the Organ Care System was 263 min (IQR 242-296 min). The overall 30-day survival rate was 100% and the 90-day survival rate was 86%. Postoperative extracorporeal membrane oxygenation was required in 3/7 (43%). CONCLUSIONS: DCD heart transplants can lead to a 23% increase in heart transplant activity and should be adopted by more institutions across the world. Already established transplant programmes with good early outcomes can start such a programme safely.

The utility of myocardial perfusion imaging before renal transplantation: a retrospective analysis.

BACKGROUND: Renal transplantation (RT) reduces morbidity and mortality in patients with end-stage renal failure. Myocardial perfusion imaging provides prognostic information in patients with renal failure, but its role before transplantation remains unclear. We performed a retrospective review assessing the prognostic value of technetium-99m sestamibi myocardial perfusion imaging at a tertiary UK centre. PATIENTS AND METHODS: We included scans performed between 2005 and 2012. Available scans were reanalysed to calculate the semiquantitative summed scores: sum rest score (SRS), sum stress score (SSS), sum difference score and sum motion score (SMS). Kaplan-Meier survival estimates assessed all-cause mortality and cardiac events according to scan findings, transplant decision and SSS. Cox-proportional hazards tested for an association between clinical/scan variables and all-cause mortality, and combined all-cause mortality/cardiovascular (CV) events. RESULTS: One hundred and thirty-eight scans were identified with complete follow-up. During a median 40.4-month follow-up, 21 patients died, with 11 nonfatal CV events. There was no significant difference between groups according to scan findings for mortality (log-rank P=0.17) or mortality/CV events (P=0.06). An SSS greater than 8 was associated with higher mortality and CV events combined (P=0.028). An abnormal baseline ECG [hazard ratio (HR): 16.1] and higher SRS (HR: 2.3) were associated independently with higher mortality; an abnormal ECG (HR: 3.4) also predicted higher cardiac events/mortality. CONCLUSION: Moderate to severe perfusion defects by SSS were associated with higher mortality and CV events. Higher SRS was associated independently with increased mortality on multivariable analysis, highlighting a key role for semiquantitative analysis methods for risk stratification. An abnormal ECG was associated strongly with both endpoints, and may be a useful screening tool to select patients for further investigation.

Heart failure - what's new and what's changed?

Physicians responsible for the care of patients with heart failure due to left ventricular systolic dysfunction have access to a broad range of evidence-based treatments that prolong life and reduce symptoms. In spite of the significant progress made over the last four decades, there is an ongoing need for novel therapies to treat a condition that is associated with stubbornly high morbidity and mortality. In this article, we discuss the findings of SERVE-HF, a randomised controlled trial of adaptive servo-ventilation in patients with left ventricular systolic dysfunction, as well as EMPA-REG, a study of the effects of a novel diabetic agent that may be of greater interest to heart failure specialists than diabetologists. We also examine further analyses of the groundbreaking PARADIGM-HF trial, which attempt to answer some of the unresolved questions from the original study of the first combined angiotensin-receptor blocker and neprilysin inhibitor, sacubitril valsartan. The recently published National Institute for Health and Care Excellence guidelines for the management of acute heart failure and plans to introduce best practice tariffs bring into focus the need for well-organised, multidisciplinary care. We discuss the challenges involved in developing and delivering a specialist service that meets the needs of a growing population of patients living with heart failure.

Acute fulminant necrotizing eosinophilic myocarditis: early diagnosis and treatment.

Necrotizing eosinophilic myocarditis is a rare but potentially fatal condition that requires prompt recognition and treatment. We describe a case of a young athlete presenting with chest pain and breathlessness, with evidence of rapidly deteriorating cardiac function. The condition was successfully treated with corticosteroids, with no evidence of residual myocardial damage. This is the first reported case to demonstrate the utility of cardiac magnetic resonance imaging for diagnosis and monitoring response to treatment. It also highlights the value of endomyocardial biopsy in establishing a tissue diagnosis in cases of fulminant myocarditis, in order to direct treatment appropriately.

Heart failure - what's new and what's changed?

Physicians responsible for the care of patients with heart failure due to left ventricular systolic dysfunction have access to a broad range of evidence-based treatments that prolong life and reduce symptoms. In spite of the significant progress made over the last four decades, there is an ongoing need for novel therapies to treat a condition that is associated with stubbornly high morbidity and mortality. In this article, we discuss the findings of SERVE-HF, a randomised controlled trial of adaptive servo-ventilation in patients with left ventricular systolic dysfunction, as well as EMPA-REG, a study of the effects of a novel diabetic agent that may be of greater interest to heart failure specialists than diabetologists. We also examine further analyses of the groundbreaking PARADIGM-HF trial, which attempt to answer some of the unresolved questions from the original study of the first combined angiotensin-receptor blocker and neprilysin inhibitor, sacubitril valsartan. The recently published National Institute for Health and Care Excellence guidelines for the management of acute heart failure and plans to introduce best practice tariffs bring into focus the need for well-organised, multidisciplinary care. We discuss the challenges involved in developing and delivering a specialist service that meets the needs of a growing population of patients living with heart failure.