Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 100
Filter
1.
Transplantation ; 103(2): 336-343, 2019 02.
Article in English | MEDLINE | ID: mdl-29757910

ABSTRACT

BACKGROUND: Heart transplantation (HTx) remains the most effective long-term treatment for advanced heart failure. Primary graft dysfunction (PGD) continues to be a potentially life-threatening early complication. In 2014, a consensus statement released by International Society for Heart and Lung Transplantation (ISHLT) established diagnostic criteria for PGD. We studied the incidence of PGD across the United Kingdom. METHODS: We analyzed the medical records of all adult patients who underwent HTx between October 2012 and October 2015 in the 6 UK heart transplant centers Preoperative donor and recipient characteristics, intraoperative details, and posttransplant complications were compared between the PGD and non-PGD groups using the ISHLT definition. Multivariable analysis was performed using logistic regression. RESULTS: The incidence of ISHLT PGD was 36%. Thirty-day all-cause mortality in those with and without PGD was 31 (19%) versus 13 (4.5%) (P = 0.0001). Donor, recipient, and operative factors associated with PGD were recipient diabetes mellitus (P = 0.031), recipient preoperative bilateral ventricular assist device (P < 0.001), and preoperative extracorporeal membranous oxygenation (P = 0.023), female donor to male recipient sex mismatch (P = 0.007), older donor age (P = 0.010), and intracerebral haemorrhage/thrombosis in donor (P = 0.023). Intraoperatively, implant time (P = 0.017) and bypass time (P < 0.001) were significantly longer in the PGD cohort. Perioperatively, patients with PGD received more blood products (P < 0.001). Risk factors identified by multivariable logistic regression were donor age (P = 0.014), implant time (P = 0.038), female: male mismatch (P = 0.033), recipient diabetes (P = 0.051) and preoperative ventricular assist device/extracorporeal membranous oxygenation support (P = 0.012). CONCLUSIONS: This is the first national study to examine the incidence and significance of PGD after HTx using the ISHLT definition. PGD remains a frequent early complication of HTx and is associated with increased mortality.


Subject(s)
Heart Transplantation/adverse effects , Primary Graft Dysfunction/epidemiology , Adult , Blood Transfusion , Female , Heart-Lung Transplantation , Humans , Incidence , Logistic Models , Male , Middle Aged , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/therapy , Retrospective Studies , Risk Factors , United Kingdom
2.
Eur Heart J Cardiovasc Imaging ; 20(2): 199-208, 2019 02 01.
Article in English | MEDLINE | ID: mdl-29668926

ABSTRACT

Aims: The need for right ventricular assist device (RVAD) support after left ventricular assist device (LVAD) therapy is associated with increased morbidity and mortality. We used 2D echocardiographic strain analysis to assess right atrial (RA) and right ventricular (RV) mechanics and predict the need for RV mechanical support after LVAD implantation. Methods and results: Seventy advanced chronic heart failure (ACHF) patients [59 male, age 47 ± 12 years, 79% dilated cardiomyopathy, left ventricular ejection fraction 23 ± 10%] received continuous-flow LVAD as a bridge to transplantation over an 18 month period. A retrospective analysis of RV and RA strain and right heart dyssynchrony was performed comparing those requiring RVAD (20%, n = 14) with those who did not (non-RVAD 80%, n = 56). One-year survival was significantly lower in the RVAD group (50% vs. 79%; P < 0.03). Independent predictors of RVAD support were: low peak RA longitudinal strain (RALS) [odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.37-2.0; P = 0.03], low RV free-wall longitudinal strain (RVFWLS) (OR 1.3, 95% CI 1.03-2.3; P = 0.04), and degree of intra-RV dyssynchrony (DRVFW-IVS, OR 1.3, 95% CI 1.02-1.3; P = 0.04). Conclusion: In LVAD recipients needing RVAD support, there was lower RALS and RVFWLS in addition to greater RV free-wall mechanical delay. We conclude that RA and RV strain and dyssynchrony analysis have the potential to add incremental value to the pre-VAD-implantation assessment made using conventional echo measurements.


Subject(s)
Echocardiography/methods , Heart Atria/diagnostic imaging , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Heart Failure/therapy , Heart-Assist Devices , Ventricular Dysfunction, Right/diagnostic imaging , Female , Heart Atria/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Ventricular Dysfunction, Right/physiopathology
3.
Interact Cardiovasc Thorac Surg ; 28(4): 594-601, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30351360

ABSTRACT

OBJECTIVES: Left ventricular assist devices are funded in the UK exclusively as a bridge to transplant (BTT). However, patients who potentially could receive a transplant may develop reversible contraindications to transplant. Bridge to candidacy (BTC) has sometimes been controversial, given the uncertain clinical efficacy of BTC and the risk that reimbursement could be denied. We analysed the UK ventricular assist device database to understand how common BTC was and to assess patient survival rates and incidences of transplants. METHODS: We identified BTC implants in patients with pulmonary hypertension, chronic kidney disease and obesity using the UK guidelines for heart transplants. RESULTS: A total of 306 of 540 patients had complete data and 157 were identified as BTC (51%). Overall, there was no difference in survival rates between patients designated as BTC and those designated at BTT (71.9 vs 72.9% at 1 year, respectively; P = 0.82). However, the survival rate was lower at all time points in those with an estimated glomerular filtration rate (eGFR) <40 and in patients with a body mass index (BMI) >32 up to 1-year postimplant. There were no significant differences in the incidence of transplant between patients who were BTC and BTT or for any subgroup up to 5 years. However, we noted a diverging trend towards a lower cumulative incidence of transplant for patients with a BMI >32. CONCLUSIONS: BTC is common in the UK and appears clinically effective, given that the survival rates and the incidence of transplants were comparable with those for BTT. Patients with a high BMI have a worse survival rate through to 1 year and a trend for a lower incidence of a transplant. Patients with a low eGFR also have a worse survival rate, but a similar proportion received transplants.


Subject(s)
Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices , Transplant Recipients , Adult , Female , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Male , Middle Aged , Survival Rate/trends , Treatment Outcome , United Kingdom/epidemiology
4.
Eur J Cardiothorac Surg ; 53(6): 1135-1143, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29370400

ABSTRACT

OBJECTIVES: The optimum time after brainstem death (BSD) at which to assess the function of donor hearts is unknown. We hypothesized that a longer interval may be associated with a higher transplantation rate due to improved function. METHODS: Data were obtained from the UK Transplant Registry for the period between April 2010 and March 2015. The time when fixed dilated pupils were first noted in the donor was considered as the time of BSD. Retrieval was defined as the time when the abdominal organs were surgically perfused. RESULTS: BSD to retrieval duration was available for 1947 donors, of which 458 (24%) donated their heart. In the univariable analysis (not adjusting other donor risk factors), evidence was available to suggest that the BSD to cardiac assessment duration had a non-linear association with heart utilization (P < 0.0001). Adjusting for donor risk factors, the relationship remained with longer intervals being associated with increased transplantation (P = 0.0056). The modelled probability of heart utilization had a similar pattern to the observed rate of heart utilization. However, the probability of heart donation began to plateau after approximately 48 h. The analysis of the subset of donors attended by a cardiothoracic retrieval team showed a similar pattern. CONCLUSIONS: These data suggest that time interval from BSD to organ retrieval influences the heart retrieval rate. When the sole reason for declining a donor heart is poor function, a period of further observation and optimization up to 2 days should be considered.


Subject(s)
Brain Death/physiopathology , Heart Transplantation , Heart/physiology , Tissue and Organ Procurement , Adult , Female , Heart Transplantation/mortality , Heart Transplantation/statistics & numerical data , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Tissue Donors/statistics & numerical data , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/statistics & numerical data , Transplant Recipients/statistics & numerical data
5.
ESC Heart Fail ; 4(4): 660-664, 2017 11.
Article in English | MEDLINE | ID: mdl-29154424

ABSTRACT

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.


Subject(s)
Computed Tomography Angiography/methods , Early Diagnosis , Echocardiography/methods , Eosinophilia/diagnosis , Magnetic Resonance Imaging, Cine/methods , Myocarditis/diagnosis , Myocardium/pathology , Acute Disease , Biopsy , Diagnosis, Differential , Electrocardiography , Eosinophilia/therapy , Humans , Male , Myocarditis/therapy , Necrosis/diagnosis , Necrosis/therapy , Young Adult
6.
Emerg Med J ; 34(12): 842-850, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29127102

ABSTRACT

Advances in left ventricular assist device (LVAD) therapy have resulted in increasing numbers of adult LVAD recipients in the community. However, device failure, stroke, bleeding, LVAD thrombosis and systemic infection can be life-threatening emergencies. Currently, four LVAD systems are implanted in six UK transplant centres, each of which provides device-specific information to local emergency services. This has resulted in inconsistent availability and content of information with the risks of delayed or inappropriate decision-making. In order to improve patient safety, a consortium of UK healthcare professionals with expertise in LVADs developed universally applicable prehospital emergency algorithms. Guidance was framed as closely as possible on the standard ABCDE approach to the assessment of critically ill patients.


Subject(s)
Algorithms , Ambulances , Emergency Medical Services/standards , Emergency Treatment/standards , Heart Failure/therapy , Heart-Assist Devices , Emergencies , Equipment Failure , Humans , United Kingdom
8.
Eur J Cardiothorac Surg ; 50(2): 269-73, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27107045

ABSTRACT

OBJECTIVES: Advanced chronic heart failure (ACHF) is progressive with poor prognosis and quality of life (QoL). Heart transplantation (HTx) is an effective treatment for ACHF, but is limited by scarcity of donor hearts. Left ventricular assist device (LVAD) support is a useful bridging therapy, and short- and medium-term outcomes have improved. We investigated QoL in patients assessed for HTx, awaiting HTx and after HTx. METHODS: We carried out a cross-sectional survey across four groups: Group 1-patients assessed for HTx, Group 2-patients listed for HTx on medical therapy, Group 3-patients supported with LVAD and Group 4-patients after HTx. Two questionnaires, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol dimensions (EQ-5D), were administered in all adult HTx centres in the UK. Scores calculated for the KCCQ and EQ-5D were compared. RESULTS: Three hundred and eighty-six patients completed questionnaires: 194 in Group 1, 28 in Group 2, 82 in Group 3 and 82 in Group 4. Patients after HTx reported the best QoL [KCCQ overall summary score: mean 73.0 (SD 27.2)]; patients with LVAD reported better QoL than those being assessed for HTx and those listed for HTx on medical therapy [overall summary score; LVAD: 52.6 (22.0), Listed on medical therapy: 33.3 (21.1), ASSESSMENT: 35.5 (21.5)]. Similarly, EQ-5D scores were highest in patients after HTx [HTx: mean 0.74 (0.27); LVAD: 0.58 (0.26), Listed on medical therapy: 0.44 (0.27), ASSESSMENT: 0.50 (SD 0.30)]. CONCLUSIONS: Patients supported with LVAD had a significantly better QoL than those awaiting HTx without LVAD support, although HTx patients reported the best QoL.


Subject(s)
Heart Failure/psychology , Heart Transplantation , Heart-Assist Devices , Quality of Life , Adult , Cross-Sectional Studies , Female , Follow-Up Studies , Heart Failure/surgery , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Surveys and Questionnaires , Treatment Outcome
9.
Artif Organs ; 40(6): 549-60, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26611518

ABSTRACT

The aim of this study was to elucidate the dynamic characteristics of the Thoratec HeartMate II (HMII) and the HeartWare HVAD (HVAD) left ventricular assist devices (LVADs) under clinically representative in vitro operating conditions. The performance of the two LVADs were compared in a normothermic, human blood-filled mock circulation model under conditions of steady (nonpulsatile) flow and under simulated physiologic conditions. These experiments were repeated using 5% dextrose in order to determine its suitability as a blood analog. Under steady flow conditions, for the HMII, approximately linear inverse LVAD differential pressure (H) versus flow (Q) relationships were observed with good correspondence between the results of blood and 5% dextrose under all conditions except at a pump speed of 9000 rpm. For the HVAD, the corresponding relationships were inverse curvilinear and with good correspondence between the blood-derived and 5% dextrose-derived relationships in the flow rate range of 2-6 L/min and at pump speeds up to 3000 rpm. Under pulsatile operating conditions, for each LVAD operating at a particular pump speed, an counterclockwise loop was inscribed in the HQ domain during a simulated cardiac cycle (HQ loop); this showed that there was a variable phase relationship between LVAD differential pressure and LVAD flow. For both the HMII and HVAD, increasing pump speed was associated with a right-hand and upward shift of the HQ loop and simulation of impairment of left ventricular function was associated with a decrease in loop area. During clinical use, not only does the pressure differential across the LVAD and its flow rate vary continuously, but their phase relationship is variable. This behavior is inadequately described by the widely accepted representation of a plot of pressure differential versus flow derived under steady conditions. We conclude that the dynamic HQ loop is a more meaningful representation of clinical operating conditions than the widely accepted steady flow HQ curve.


Subject(s)
Heart-Assist Devices , Pulsatile Flow , Computer Simulation , Hemodynamics , Humans , Hydrodynamics , Models, Cardiovascular , Pressure , Ventricular Function, Left
10.
J Thorac Cardiovasc Surg ; 150(6): 1651-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26318358

ABSTRACT

OBJECTIVE: The outcomes of ventricular assist device therapy remain limited by right ventricular failure. We sought to define the predictors and evaluate the outcomes of right ventricular failure requiring right ventricular assist device support after long-term continuous-flow left ventricular assist device implantation. METHODS: Records of all continuous-flow left ventricular assist device recipients for the last 10 years were analyzed, including patients on preoperative intra-aortic balloon pump, extracorporeal membrane oxygenation, and short-term ventricular assist device support. Perioperative clinical, echocardiographic, hemodynamic, and laboratory data of continuous-flow left ventricular assist device recipients requiring right ventricular assist device support (right ventricular assist device group) were compared with the rest of the patient cohort (control group). RESULTS: Between July 2003 and June 2013, 152 patients underwent continuous-flow left ventricular assist device implantation as a bridge to transplantation. The overall postoperative incidence of right ventricular assist device support was 23.02% (n = 35). Right ventricular assist device implantation did not significantly affect eventual transplantation (P = .784) or longer-term survival (P = .870). Preoperative right ventricular diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), previous sternotomy (P = .002), preoperative short-term mechanical support (P = .005), left atrial diameter (P = .014), female gender (P = .020), age (P = .027), and preoperative bilirubin levels (P = .031) were univariate predictors of right ventricular assist device implantation. Multivariate analysis revealed lesser tricuspid annular plane systolic excursion (P = .013; odds ratio, 0.613; 95% confidence interval, 0.417-0.901) and smaller left atrial diameter (P = .007; odds ratio, 0.818; 95% confidence interval, 0.707-0.947) as independent predictors of right ventricular assist device implantation. Receiver operating characteristic curve of tricuspid annular plane systolic excursion yielded an area under the curve of 0.85 (95% confidence interval, 0.781-0.923), with cutoff tricuspid annular plane systolic excursion less than 12.5 mm having 84% sensitivity and 75% specificity. CONCLUSIONS: Lesser tricuspid annular plane systolic excursion and smaller left atrial diameter are independent predictors of the need for right ventricular assist device support after continuous-flow left ventricular assist device implantation. Right ventricular assist device implantation does not adversely affect eventual transplantation or survival after continuous-flow left ventricular assist device implantation.


Subject(s)
Heart-Assist Devices , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Right/physiopathology , Adult , Extracorporeal Membrane Oxygenation , Female , Humans , Intra-Aortic Balloon Pumping , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate , Treatment Outcome
11.
Am J Cardiol ; 116(3): 447-51, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-26048854

ABSTRACT

Giant cell myocarditis (GCM) is an aggressive inflammatory myocardial disease. Immunosuppression is an effective treatment for some cases. However, the duration of action of agents such as muromonab CD3 is short and others such as the calcineurin inhibitors may lead to renal failure. Here we describe the outcome of a novel approach to treatment using rabbit anti-thymocyte globulin (RATG). A retrospective analysis of 6 patients treated with RATG for GCM was performed. Diagnosis was confirmed by endomyocardial biopsy, and RATG was administered with a high dose of corticosteroids. None of the patients had cytokine release syndrome or leukopenia, and 5 had thrombocytopenia (2 of them severe). Only 1 had a serious bleeding event that occurred after implantation of mechanical circulatory support. None developed impaired renal function after the treatment. Five were successfully discharged home with an increase in global left ventricular ejection fraction of 29%. Four are currently alive without recurrent disease, 1 of them after heart transplantation, with a mean follow-up of 970 days (423 to 1,875 days), left ventricular ejection fraction of 53%, and all in current New York Heart Association Classification class ≤II. Only 1 case had GCM recurrence. There were 2 deaths: one because of intracranial bleeding after mechanical circulatory support implantation and the other caused by primary graft dysfunction. In conclusion, patients with GCM can be successfully immunosuppressed with RATG and corticosteroids, thereby avoiding renal impairment. Early thrombocytopenia is the main adverse event. Larger cohorts of patients are necessary to compare the different immunosuppressant strategies available for GCM in a randomized fashion.


Subject(s)
Antilymphocyte Serum/therapeutic use , Giant Cells/pathology , Immunosuppression Therapy/methods , Myocarditis/drug therapy , Myocardium/pathology , Adult , Biopsy , Follow-Up Studies , Humans , Immunologic Factors/therapeutic use , Male , Middle Aged , Myocarditis/diagnosis , Retrospective Studies , Treatment Outcome , Young Adult
12.
PLoS One ; 10(5): e0128033, 2015.
Article in English | MEDLINE | ID: mdl-26020944

ABSTRACT

BACKGROUND: There are few data relating to sirolimus overdose in the medical literature. Our objectives were to describe all cases of overdose with sirolimus reported to Swiss, German and Austrian Poisons Centres between 2002-2013. METHODS: An observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose. RESULTS: Five cases of acute sirolimus overdose were reported--three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range. CONCLUSIONS: Acute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.


Subject(s)
Drug Overdose/diagnosis , Fever/diagnosis , Gastroenteritis/diagnosis , Sirolimus/adverse effects , Suicide, Attempted/prevention & control , Adolescent , Alkaline Phosphatase/blood , Child, Preschool , Cholesterol/blood , Drug Overdose/blood , Drug Overdose/physiopathology , Female , Fever/blood , Fever/chemically induced , Fever/physiopathology , Gastroenteritis/blood , Gastroenteritis/chemically induced , Gastroenteritis/physiopathology , Humans , Infant , Male , Middle Aged , Retrospective Studies
14.
Hum Gene Ther ; 26(5): 293-304, 2015 May.
Article in English | MEDLINE | ID: mdl-25914929

ABSTRACT

Gene therapy has been applied to cardiovascular disease for over 20 years but it is the application to heart failure that has generated recent interest in clinical trials. There is laboratory and early clinical evidence that delivery of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy is beneficial for heart failure and this therapy could become the first positive inotrope with anti-arrhythmic properties. In this review we will discuss the rationale for SERCA2a gene therapy as a viable strategy in heart failure, review the published data, and discuss the ongoing clinical trials, before concluding with comments on the future challenges and potential for this therapy.


Subject(s)
Genetic Therapy , Heart Failure/genetics , Heart Failure/therapy , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Animals , Clinical Trials as Topic , Gene Transfer Techniques , Genetic Vectors/genetics , Heart Failure/metabolism , Humans , Research Design , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Translational Research, Biomedical
15.
Interact Cardiovasc Thorac Surg ; 20(6): 755-60, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25796276

ABSTRACT

OBJECTIVES: Traditionally, patients on extracorporeal life support (ECLS) are sedated and mechanically ventilated and therefore prone to complications related to immobility and ventilation. We adopted this 'Awake ECLS' strategy for the patients with refractory cardiogenic shock (RCS) as a bridge to decision. METHODS: Sixty-eight patients with RCS were supported by ECLS (All veno-arterial) in years 2010-2014. Patients that could not survive 24 h after ECLS implantation (9 patients) were excluded from the study. Study population constituted 59 patients-'Awake' group (n = 18; maintained awake without intubation) and 'Control' group (n = 41; intubated and required mechanical ventilation). RESULTS: Nine (50%) patients were awake at implantation, with 5 of them remaining free of sedation and ventilator support through to explantation. Nine patients were ventilated at the time of implantation but subsequently extubated and remained non-intubated and ventilator free. Post-ECLS survival at 1 month was 78 and 42% while the survival to discharge was 78 and 37% in awake and control group, respectively. CONCLUSIONS: ECLS as a bridge to decision in RCS is effective in restoring adequate systemic perfusion and recovering end-organ function. ECLS can be initiated in awake patients with RCS and patients can be awakened on ECLS. The 'awake ECLS' strategy may avoid complications related to mechanical ventilation, sedation and immobilization. RCS patients supported on ECLS without severe metabolic acidosis, multiorgan failure, intra-aortic balloon pump or uncertain neurological status are more likely to be weaned from the ventilator. Patients that are awake at the time of ECLS implantation are more likely to remain awake during ECLS.


Subject(s)
Extracorporeal Circulation/methods , Life Support Care/methods , Shock, Cardiogenic/therapy , Wakefulness , Adult , Airway Extubation , Extracorporeal Circulation/adverse effects , Extracorporeal Circulation/mortality , Female , Humans , Hypnotics and Sedatives/therapeutic use , Immobilization , Intubation, Intratracheal , Kaplan-Meier Estimate , Male , Middle Aged , Recovery of Function , Respiration, Artificial , Retrospective Studies , Risk Factors , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/mortality , Shock, Cardiogenic/physiopathology , Time Factors , Treatment Outcome , Ventilator Weaning
16.
Transplantation ; 99(9): 1919-25, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25742423

ABSTRACT

BACKGROUND: Heart transplantation is an established treatment for advanced heart failure. Primary allograft dysfunction (PGD) is reported in up to 40% of transplants and is associated with a poor outcome. METHODS: As part of Heart Evaluation and Retrieval for Transplantation study, an investigation of the assessment of donor hearts for transplantation, we proposed a clinical definition for cardiac PGD comprising severely impaired systolic function affecting one or both ventricles accompanied by hypotension, low cardiac output, and high filling pressures occurring in the first 72 hours (in the absence of hyper acute rejection and technical surgical factors, such as cardiac tamponade). Here, we examine the prospective application of this definition to 290 heart transplants. We compared the clinical outcome of PGD and non-PGD cases. RESULTS: Ninety-four of 290 transplants developed PGD (32.4%). Inotrope use (score) was higher in the PGD group at 24, 48, and 72 hours after transplantation (P < 0.01). In the PGD group, there was a greater requirement for, intra-aortic balloon pump (50% vs 15%, P < 0.01), mechanical support (27% vs 0%, P < 0.01), and renal replacement therapy (61% vs 26%, P < 0.01). Intensive care stay was longer for recipients with PGD (median 14 vs 5 days, P < 0.01) and early mortality was higher (37% vs 4% at 30 days, 42% vs 8% at 1 year, P < 0.01). CONCLUSIONS: In conclusion, our definition of PGD could be applied in a national multicenter study, and the cases it defined had more frequent complications and higher mortality.


Subject(s)
Cardiac Output, Low/classification , Cardiac Output, Low/diagnosis , Heart Failure/surgery , Heart Transplantation/adverse effects , Primary Graft Dysfunction/classification , Primary Graft Dysfunction/diagnosis , Terminology as Topic , Adult , Cardiac Output, Low/etiology , Cardiac Output, Low/physiopathology , Cardiac Output, Low/therapy , Cardiotonic Agents/therapeutic use , Female , Heart Failure/mortality , Heart Transplantation/mortality , Hemodynamics , Humans , Intensive Care Units , Intra-Aortic Balloon Pumping , Length of Stay , Male , Middle Aged , Predictive Value of Tests , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/physiopathology , Primary Graft Dysfunction/therapy , Prospective Studies , Renal Replacement Therapy , Reproducibility of Results , Severity of Illness Index , Time Factors , Treatment Outcome , United Kingdom
17.
Sci Transl Med ; 7(270): 270ra6, 2015 Jan 14.
Article in English | MEDLINE | ID: mdl-25589632

ABSTRACT

The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.


Subject(s)
Alleles , Connectin/genetics , Heart/physiology , Mutation , Transcription, Genetic , Adolescent , Adult , Aged , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Cohort Studies , Connectin/physiology , Exons , Genetic Variation , Healthy Volunteers , Heart Failure/genetics , Heart Failure/therapy , Humans , Immunoglobulins/metabolism , Middle Aged , Protein Isoforms/genetics , Protein Isoforms/physiology , Young Adult
18.
Artif Organs ; 39(3): 212-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25175547

ABSTRACT

The purpose of this study was to evaluate gender differences regarding outcome after continuous-flow left ventricular assist device (cfLVAD) implantation. The study was a retrospective review of prospectively collected data. Included were 24 consecutive female cfLVAD recipients and 24 male recipients (62.5% HeartMate II, 37.5% HeartWare) who received their devices between July 2007 and May 2013. Subjects were matched using propensity score analysis based on age, diagnosis, body surface area, preoperative mechanical circulatory support, heart failure severity score (INTERMACS class), and comorbidities. Female patients were significantly sicker before operation. After propensity score matching, there were no statistically significant differences in demographics or clinical baseline characteristics between male and female LVAD recipients. Also, there was a trend towards a longer postoperative intensive care unit stay in the female group (median 9 days [interquartile range 5-17] versus 15 days [interquartile range 8-33]; P < 0.061) and higher postoperative bilirubin values (median 14 mmol/L [interquartile range 10-17] versus 21 mmol/L [interquartile range 13-30]). However, there were no significant differences between the two groups in terms of outcome (P < 0.569). The overall survival was comparable between the two groups (log rank P < 0.389). Half (50%) of female patients required inotropic support for more than 7 days compared with 21.7% in the male group (P < 0.048). Half (50%) of female recipients required short-term postoperative right ventricular assist device implantation compared with 16.7% in the male group (P < 0.014). In conclusion, cfLVAD implantation as a bridge to transplantation is associated with longer duration of inotropic support and higher requirement for postoperative mechanical right ventricular support in women with similar survival rates. Further studies are required to identify additional demographic and clinical factors that modulate outcomes and will enhance the ability to risk-stratify cfLVAD recipients.


Subject(s)
Heart Failure/mortality , Heart Failure/surgery , Heart Transplantation/methods , Heart-Assist Devices , Risk Adjustment/methods , Waiting Lists , Adult , Cohort Studies , Female , Heart Failure/diagnosis , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , Severity of Illness Index , Sex Factors , Statistics, Nonparametric , Survival Rate , Time Factors , Treatment Outcome
19.
Artif Organs ; 39(2): 118-25, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24841499

ABSTRACT

The Synergy Micro-pump is the smallest implantable left ventricular assist device (LVAD) and provides partial flow support up to 4.25 L/min. It was shown that early intervention with this device can provide substantial benefits to patients with severe heart failure not yet sick enough for a full-support LVAD. However, as it can be inserted via small incisions with no need for sternotomy or cardiopulmonary bypass, it might be beneficial for selected high-risk patients. The aim of this study was to evaluate the efficacy of the Synergy Micro-pump in patients in INTERMACS class 1-2. From February 2012 to August 2013, 13 patients with severe heart failure were supported with the Synergy Pocket Micro-pump. Patients were divided into two groups according to INTERMACS class: the high-risk group (INTERMACS class 1-2) and the low-risk group (INTERMACS class 3-4). There were seven patients in INTERMACS class 1-2 and six in INTERMACS class 3-4. Patient demographics, perioperative characteristics, and postoperative outcomes were compared. There were no statistically significant differences in patient demographics, and mean support time was 108 ± 114 days in the high-risk group and 238 ± 198 days in the low-risk group. Also, there were no significant differences in perioperative characteristics or in the rate of postoperative adverse events. The overall survival was comparable between the two groups (one late death in each group, log-rank P = 0.608). Two patients from the high-risk group were upgraded to a full-support LVAD (P = 0.462) after 65 ± 84.9 days of mean support. One patient from the high-risk group and two patients from the low-risk group were successfully transplanted (P = 0.559). The use of the Synergy Micro-pump in INTERMACS 1-2 patients is feasible and is associated with similar postoperative outcome as in patients in INTERMACS 3-4. Carefully selected patients with severe heart failure could benefit due to the small size of the pump; however, further studies and medium-term follow-up are required.


Subject(s)
Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices , Adult , Cardiopulmonary Bypass , Female , Follow-Up Studies , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Humans , Male , Middle Aged , Survival Analysis
20.
Ann Thorac Cardiovasc Surg ; 21(2): 151-6, 2015.
Article in English | MEDLINE | ID: mdl-25017117

ABSTRACT

PURPOSE: Despite their efficacy, LVADs remain associated with serious complications. The relationship between haemodynamic changes during support and outcome remains inadequately characterised. This association was investigated in LVAD recipients undergoing prolonged support. METHODS: Forty patients receiving LVAD therapy for >2 years were reviewed retrospectively (mean support duration was 38.62 ± 15.28). Pre- and on-LVAD haemodynamic data were assessed in three groups: (1) those receiving ongoing support (n = 24); (2) those who underwent cardiac transplantation (n = 4); (3) those who died during support (n = 12). RESULTS: For group 1 and 2, LVAD support achieved a decrease in mean PAP, mean PCWP, TPG, and PVR and an increase in thermodilution blood flow (TBF) with significance at ≤5% level. For group 3, there were non-significant changes in TPG and PVR at the 5% level but for mean PAP, mean PCWP, and TBF the changes were similar to Groups 1 and 2 with significance at ≤5% level. Aggregated data from all three groups showed a 58% increase in TBF on LVAD support. CONCLUSION: Highly significant and favourable haemodynamic changes were found. However, group 3 did not undergo decrease in TPG and PVR possibly because of suboptimal LVAD flow, right heart dysfunction and unavoidable prolongation of support.


Subject(s)
Heart Failure/surgery , Heart-Assist Devices , Hemodynamics , Ventricular Function, Left , Adolescent , Adult , Aged , England , Female , Heart Failure/diagnosis , Heart Failure/mortality , Heart Failure/physiopathology , Heart-Assist Devices/adverse effects , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prosthesis Design , Pulmonary Artery/physiopathology , Pulmonary Circulation , Pulmonary Wedge Pressure , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Resistance , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...