Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.

BACKGROUND: Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. METHODS: The recipients were patients at St Vincent's Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. FINDINGS: Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3-8·1 mmol/L for patient 1, 6·79-6·48 mmol/L for patient 2, and 7·6-7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6-3·6 mmol/L, 2·8-2·3 mmol/L, and 2·69-2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. INTERPRETATION: Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. FUNDING: NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.

Accelerated graft dysfunction in heart transplant patients with persistent atrioventricular conduction block.

AIMS: Bradyarrhythmia following heart transplantation is common-∼7.5-24% of patients require permanent pacemaker (PPM) implantation. While overall mortality is similar to their non-paced counterparts, the effects of chronic right ventricular pacing (CRVP) in heart transplant patients have not been studied. We aim to examine the effects of CRVP on heart failure and mortality in heart transplant patients. METHODS AND RESULTS: Records of heart transplant recipients requiring PPM at St Vincent's Hospital, Sydney, Australia between January 1990 and January 2015 were examined. Patient's without a right ventricular (RV) pacing lead or a follow-up time of <1 year were excluded. Patients with pre-existing abnormal left ventricular function (<50%) were analysed separately. Patients were grouped by pacing dependence (100% pacing dependent vs. non-pacing dependent). The primary endpoint was clinical or echocardiographic heart failure (<35%) in the first 5 years post-PPM. Thirty-three of 709 heart transplant recipients were studied. Two patients had complete RV pacing dependence, and the remaining 31 patients had varying degrees of pacing requirement, with an underlying ventricular escape rhythm. The primary endpoint occurred significantly more in the pacing-dependent group; 2 (100%) compared with 2 (6%) of the non pacing dependent group (P < 0.0001 by log-rank analysis, HR = 24.58). Non-pacing-dependent patients had reversible causes for heart failure, unrelated to pacing. In comparison, there was no other cause of heart failure in the pacing-dependent group. CONCLUSIONS: Permanent atrioventricular block is rare in the heart transplant population. We have demonstrated CRVP as a potential cause of accelerated graft failure in pacing-dependent heart transplant patients.

Aortic valve replacement in octogenarians.

BACKGROUND: With improved life expectancy more octogenarians now present with aortic valve disease. Cardiac surgery in this group of patients has previously been considered high risk due to co-morbidities and challenges of rehabilitation. This study seeks to challenge the concept of octogenarian cardiac surgery "unsuitability" by analysing operative outcomes and long term survival following aortic valve replacement. METHODS: Eighty-seven consecutive patients undergoing aortic valve replacement between 2000 and 2009 at St Vincent's Hospital were retrospectively identified. Statistical analysis was performed using SPSS (version 15 and 19). RESULTS: The average age was 82.7 ± 2.4 years. The mean logistic EuroSCORE was 18.86 ± 14.11. Post-operatively, four patients required insertion of a permanent pacemaker (4.6%) and five patients had a myocardial infarction (5.8%). In-hospital mortality was 3.4%. Follow-up was 93.1% complete. One-year survival was 92.9%, three-year survival was 86.7% and five-year survival was 75.0%. At follow-up 98.1% of patients were New York Heart Association (NYHA) Class I or II. CONCLUSIONS: Results were excellent despite reasonable co-morbidities and Euroscore risk. Survival was impressive and the NYHA class reflected the success of the surgery in relieving the pathological aortic valve process. Patient age should not be the primary exclusion for cardiac surgery for aortic valve disease.

Cardiac surgery is successful in heart transplant recipients.

BACKGROUND: Improved survival of heart transplant (HTx) recipients and increased acceptance of higher risk donors allows development of late pathology. However, there are few data to guide surgical options. We evaluated short-term outcomes and mortality to guide pre-operative assessment, planning, and post-operative care. METHODS: Single centre, retrospective review of 912 patients who underwent HTx from February 1984 - June 2012, identified 22 patients who underwent subsequent cardiac surgery. Data are presented as median (IQR). RESULTS: Indications for surgery were coronary allograft vasculopathy (CAV) (n=10), valvular disease (n=6), infection (n=3), ascending aortic aneurysm (n=1), and constrictive pericarditis (n=2). There was one intraoperative death (myocardial infarction). Hospital stay was 10 (8-21) days. Four patients (18%) returned to theatre for complications. After cardiac surgery, survival at one, five and 10 years was 91±6%, 79±10% and 59±15% with a follow-up of 4.6 (1.7-10.2) years. High pre-operative creatinine was a univariate risk factor for mortality, HR=1.028, (95%CI 1.00-1.056; p=0.05). A time dependent Cox proportional hazards model of the risk of cardiac surgery post-HTx showed no significant hazard; HR=0.87 (95%CI 0.37-2.00; p=0.74). CONCLUSIONS: Our experience shows cardiac surgery post-HTx is associated with low mortality, and confirms that cardiac surgery is appropriate for selected HTx recipients.

Normalisation of haemodynamics in patients with end-stage heart failure with continuous-flow left ventricular assist device therapy.

BACKGROUND: New generation continuous-flow left ventricular assist devices (LVADs) utilise centrifugal pumps. Data concerning their effect on patient haemodynamics, ventricular function and tissue perfusion is limited. We aimed to document these parameters following HeartWare centrifugal continuous-flow LVAD (HVAD) implantation and to assess the impact of post-operative right heart failure (RHF). METHODS: We reviewed 53 consecutive patients (mean age 49.5 ± 14.1 yrs) with HVAD implanted in the left ventricle, at St. Vincent's Hospital, Sydney, between January 2007 and August 2012. Available paired right heart catheterisation (n=35) and echocardiography (n=39) data was reviewed to assess response of invasive haemodynamics and ventricular function to LVAD support. RESULTS: A total of 28 patients (53%) were implanted from interim mechanical circulatory support. Seventeen patients (32%) required short-term post-implant veno-pulmonary artery extracorporeal membrane oxygenation. At 100 ± 61 days post-implant, mean pulmonary artery pressure and mean pulmonary capillary wedge pressure decreased from 38.8 ± 7.7 to 22.9 ± 7.7 mmHg and 28.3 ± 6.4 to 13.4 ± 5.4 mmHg respectively (p<0.001). LV end diastolic diameter decreased from 71.3 ± 12.7 to 61.1 ± 13.7 mm and LV end-systolic diameter from 62.7 ± 12.3 to 53.9 ± 14.4mm (p<0.001). Aortic regurgitation remained trivial. Serum sodium increased from 133.3 ± 5.7 to 139.3 ± 2.8 mmol/L and creatinine decreased from 109.1 ± 42.5 to 74.3 ± 26.2 µmol/L (p<0.001). Across the entire cohort, the six-month survival/transplant rate was significantly lower for RHF patients (72.2%, n=18) compared to those without (96.9%, n=35, p=0.01). CONCLUSIONS: HVAD support improves haemodynamics, LV dimensions and renal function. Following implantation with a centrifugal continuous-flow LVAD, RHF remains a significant risk with a tendency to worse outcomes in the short to medium term.

Interaction between physical activity and continuous-flow left ventricular assist device function in outpatients.

OBJECTIVE: Studies have shown that pump output by continuous-flow left ventricular assist devices (LVADs) increases with graded exercise testing. However, data on pump behavior during activities of daily living and sleep, where cardiac output requirements vary markedly, are lacking. We sought to determine pump parameters and activity levels in stable patients receiving outpatient LVAD therapy. METHODS AND RESULTS: Eleven outpatients (mean age 51 ± 14 years, 9 male) with centrifugal continuous-flow LVADs underwent monitoring of LVAD flow, heart rate (HR), energy expenditure, and physical activity over 1 week in an outpatient setting. Physical activity was recorded with the use of a combined pedometer, accelerometer, and calorimeter Sensewear armband. Pump, HR, and physical activity parameters were time matched for correlation analysis. Outpatients had an average pump flow of 5.67 ± 1.27 L/min and engaged predominately in low levels of physical activity (mean daily step count 3,249/day). Across the entire cohort, pump flow exhibited strong univariate relationships with patients' energy expenditure (r = 0.73), step count (r = 0.69), HR (r = 0.73), sleep (r = -0.89), and skin temperature (r = -0.85; P < .0001 for all). Multivariate analysis suggested that pump output was predominantly affected by recumbent position, energy expenditure and skin temperature (r(2) = 0.84; P < .0001). Pump flow and power consumption were significantly lower during sleep than during wake periods (5.48 ± 1.31 L/min vs 5.80 ± 1.26 L/min; P < .001). CONCLUSIONS: Pump output from continuous-flow LVADs is adaptive to changes in activities of daily living. Circadian variation in pump flow is mostly explained by recumbency and activity levels. Despite adequate pump flow, many LVAD patients continue to live sedentary lifestyles.

Thrombolysis for suspected intrapump thrombosis in patients with continuous flow centrifugal left ventricular assist device.

The current recommended anticoagulation regimen during continuous flow centrifugal left ventricular device support is a combination of antiplatelet therapy as well as oral anticoagulation. Despite this, pump thrombosis occurs in rare situations. We report the risk factors and nonsurgical management and outcomes of five patients implanted with continuous flow centrifugal left ventricular assist devices who displayed clinical, hemodynamic, and laboratory features of intrapump thrombosis. This information may support the use of intravenous thrombolytics for suspected pump thrombus in these newer generation devices.

Death on an LVAD-Two sides of a coin.

LVADs are increasingly being used to support patients with end stage heart failure. As such, the traditional definition of death, the absence of a pulse, requires re-examination as it is no longer clinically relevant. We present two contrasting cases of "death" on LVAD support and present some ethical issues surrounding the end of life on LVAD support.

Extra corporeal membrane oxygenation as right heart support following left ventricular assist device placement: a new cannulation technique.

Extracorporeal membrane oxygenation is an established treatment for acute respiratory failure, or low cardiac output syndrome. This can be veno-venous, in which de-oxygenated blood is drained from the venous system and oxygenated before being returned to the venous system, and veno-arterial where the re-oxygenated venous blood is returned to the arterial system. Haemorrhage, sepsis and thrombo-embolism are common and potentially lethal complications. Left ventricular assist devices are a continually evolving technology, that may be used as a bridge to transplantation or destination therapy in end-stage cardiac failure. The VentrAssist™ left ventricular assist device is a small implantable, continuous flow centrifugal pump, that is controlled and powered by a percutaneous lead. However, in these patients, right heart failure may present as an acute event following weaning from cardiopulmonary bypass (CPB), or post-operatively in the intensive care unit. Patients who do not respond to inotropes and pulmonary vasodilators may need a right ventricular assist device (RVAD). We report a successful case of right heart assist extra corporeal membrane oxygenation used as temporary right heart support in combination with a VentrAssist™ left ventricular assist device. The use of right heart assist extra corporeal membrane oxygenation to help a failing right heart during left ventricular assist device placement is not new, however, our technique describes a novel method of cannulation of the femoral vein and pulmonary trunk via a tunnelled vascular tube graft, which allows the chest to be closed whilst on right heart support, and decannulation to proceed without resternotomy. This technique has also been used successfully subsequent to this.

Permanent pacing for late-onset atrioventricular block in patients with heart transplantation: a single center experience.

INTRODUCTION: The incidence, mechanisms, clinical associations, and outcomes in patients with late-onset (>3 months) atrioventricular (AV) block following heart transplantation are not well known. This study will characterize late-onset AV block following cardiac transplantation. METHODS: We retrospectively reviewed our databases to identify patients who required pacemakers for late-onset AV block postheart and heart-lung transplantation from January 1990 to December 2007. Orthotopic heart and heart-lung transplantation were separately analyzed. RESULTS: This study included 588 adults who received cardiac transplants over a 17-year period at our center (519 orthotopic, 64 heart-lung transplants, and five heterotopic heart transplants). Of the 519 patients with orthotopic heart transplant, 39 required pacing (7.5%), 17 (3.3%) within 3 months posttransplant, 11 (2.1%) for late-onset sinus node dysfunction (SND), 11 (2.1%) for late-onset AV block. Also, five patients (7.8%) out of 64 heart-lung transplants required pacemakers, two (3.1%) for late-onset SND, three (4.7%) for late-onset AV block. None of the five patients who underwent heterotopic transplant required cardiac pacing prior to or posttransplant. CONCLUSIONS: Late-onset AV block occurs in 2.4% of patients with orthotopic heart transplant or heart-lung transplant. AV block is predominantly intermittent and, often, does not progress to permanent AV block. There are no predictable factors for its onset.

Estimating the volume of chronic pleural effusions using transesophageal echocardiography.

OBJECTIVE: To develop a simple method of quantifying the volume of chronic pleural effusions caused by heart failure using transesophageal echocardiography measurement of the maximum cross-sectional area of the pleural effusion. DESIGN: A prospective observational case series. SETTING: An operating room. PARTICIPANTS: Twenty-eight patients undergoing cardiac surgery known to have chronic pleural effusions caused by heart failure diagnosed preoperatively in whom surgical management included draining the effusion. INTERVENTIONS: Transesophageal echocardiography was in situ for clinical reasons. The drainage of all pleural effusions was performed according to clinical judgement. MEASUREMENT AND MAIN RESULT: The maximum cross-sectional area (CSA(max)) in centimeters squared of the pleural effusion on transesophageal echocardiography was recorded. The chest and pleural cavity were opened, the pleural effusion was drained, and total amount of fluid drained was recorded. The data were analyzed on a log-log plot with the conclusion that volume (V) in milliliters could be estimated from the following formula: V = 4.5 · CSA(max)(3/2). CONCLUSION: This study showed a simple way of quantifying the volume of chronic pleural effusions from heart failure in patients undergoing cardiac surgery, with potential for clinical applications.

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia.

BACKGROUND: Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice. OBJECTIVES: The purpose of this study is to provide an update on the authors' Australian clinical program and discuss lessons learned since performing the world's first series of distantly procured DCD heart transplants. METHODS: The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent's Hospital. RESULTS: Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function. CONCLUSIONS: DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors.

Outcomes of venopulmonary arterial extracorporeal life support as temporary right ventricular support after left ventricular assist implantation.

OBJECTIVES: We report our experience with temporary postoperative venopulmonary arterial extracorporeal life support as short-term right ventricular support in patients with biventricular failure undergoing HeartWare (HeartWare Inc, Framingham, Mass) left ventricular assist device implantation and compared these outcomes with isolated left ventricular assist device support and long-term biventricular assist device support. METHODS: A total of 112 consecutive patients were studied, 75 with the isolated HeartWare left ventricular assist device, 23 with a concomitant left ventricular assist device and venopulmonary arterial extracorporeal life support, and 14 with durable biventricular assist device support. The decision concerning short-term or durable biventricular support was based on the clinical characteristics, echocardiography, and hemodynamic profile. RESULTS: Patients who required venopulmonary arterial extracorporeal life support after left ventricular assist device insertion required the greatest support preoperatively and were more likely to have Interagency Registry for Mechanical Assisted Circulatory Support level 1 (left ventricular assist device 19%, venopulmonary arterial extracorporeal life support 48%, biventricular assist device 57%, P < .001). They were more likely to require preoperative mechanical support (left ventricular assist device 9%, venopulmonary arterial extracorporeal life support 43%, and biventricular assist device 29%, P < .001) or preoperative ventilation (9%, 38%, and 21%, respectively, P < .05). Preoperative echocardiographic and hemodynamic parameters were more similar to those requiring isolated left ventricular assist device, with patients requiring durable biventricular assist device support more likely to have elevated right atrial pressure (left ventricular assist device 14.3 ± 6.7 vs venopulmonary arterial extracorporeal life support 13.6 ± 4.8 vs biventricular assist device 18.7 ± 6.0 mm Hg, P < .05); right atrial/pulmonary capillary wedge pressure ratio (0.53 ± 0.23 vs 0.51 ± 0.17, vs 0.69 ± 0.22, respectively, P < .02); and tricuspid regurgitation grade (1.7 ± 1.5 vs 1.7 ± 1.6 vs 2.8 ± 1.6, respectively, P < .01). One-year survival was 84% for those with an isolated left ventricular assist device compared with 62% for those with venopulmonary arterial extracorporeal life support and 64.3% for biventricular assist device. CONCLUSIONS: In critically unwell patients requiring temporary biventricular support, planned venopulmonary arterial extracorporeal life support provides acceptable outcomes, similar to durable biventricular assist device support. Requirement for venopulmonary arterial extracorporeal life support is more determined by the level of preoperative acuity than echocardiographic or hemodynamic parameters.

VentrAssist left ventricular assist device: clinical trial results and Clinical Development Plan update.

OBJECTIVES: To summarise the primary efficacy and safety results from the first international clinical trial with the VentrAssist left ventricular assist device and to provide an update on the VentrAssisttrade mark Clinical Development Plan. METHODS: The first prospective, single-arm, multicentre international clinical trial with the VentrAssist in bridge-to-transplant patients (CE Mark trial) was conducted in Australia, UK and Norway between 2004 and 2006. The primary outcome measure was survival until transplant or being transplant-eligible at postoperative day 154. The number and status of other clinical trials in the VentrAssist Clinical Development Plan are also described. RESULTS: At the completion of the CE Mark trial, 25 of the 30 patients (83%) were transplanted or transplant-eligible. There were no unexpected safety issues and no reported uncontrolled stops of the VentrAssist pump. The Clinical Development Plan for the VentrAssist currently comprises seven clinical trials: two are completed, three are ongoing and two are ready for initiation. As of January 30th, 2007, a total of 87 patients have been implanted with the VentrAssist at 14 centres worldwide, yielding a total exposure time of more than 43 patient-years and a maximum implant duration of 2.7 years. CONCLUSIONS: The efficacy and safety data from a clinical trial of the VentrAssist were favourable and resulted in gaining European regulatory approval for this indication. Notably, the survival success rate for the VentrAssist was higher than that reported for other left ventricular assist devices. The overall number of implants with the VentrAssist has now surpassed that of any other third-generation centrifugal device.

Gastric antral patch oesophagoplasty for iatrogenic tracheo-oesophageal fistula.

Acquired tracheo-oesophageal fistula is a devastating condition, usually occurring as a late manifestation of oesophageal or other thoracic malignancies. In these cases palliation by placement of an oesophageal stent is the preferred option, but management of a large non-malignant fistula is more complex. In many patients in whom primary repair of the defects is not possible oesophagectomy may be seen as the best treatment. We present a case of a large tracheo-oesophageal fistula repaired with a gastric antral patch oesophagoplasty and intercostal muscle flap.

Nosocomial infections acquired by patients treated with extracorporeal membrane oxygenation.

BACKGROUND: Infectious complications in patients treated with extracorporeal membrane oxygenation (ECMO) are a frequent contributor to morbidity and mortality in this group. Defining the characteristics of ECMO-related infections may inform treatment decisions, including antimicrobial therapy. METHODS: A retrospective observational study in an Australian intensive care unit, including adult patients treated with ECMO for at least 48 hours, over a 3-year period. Medical records were analysed for evidence of bloodstream infections (BSIs) and wound infections (WIs) at the ECMO cannulation site or the sternum. Demographic, ECMO-related and clinical data were collected, including inpatient antibiotic usage. RESULTS: We included 98 patients in the study. The median age was 50 years (IQR, 39-57 years). The median duration of ECMO treatment was 6.6 days (IQR, 4.0-12.8 days). Twenty-four infections were diagnosed in 21 patients; eight patients were diagnosed with BSIs on ECMO, 14 developed cannulation-site WIs, and two patients developed sternal wound infections. On multivariate analysis, we found that factors that increased infection risk included immunosuppression (OR, 2.9; P = 0.04) and treatment with venoarterial (VA) ECMO (OR, 14.7; P = 0.01). Infected patients had a significantly longer duration of hospital admission than patients without BSI or WI (55 days v 30 days; P = 0.03). Prior antibiotic use did not appear to be protective against subsequent infection. CONCLUSIONS: Infectious complications are common in ECMO patients and are associated with longer durations of hospital admission. Isolated pathogens were predominantly hospital-acquired Gram-negative bacteria and yeasts. Immunosuppression and treatment with VA ECMO were found to be specific risk factors for infection.

Longitudinal structural, functional, and cellular myocardial alterations with chronic centrifugal continuous-flow left ventricular assist device support.

BACKGROUND: Left ventricular assist device (LVAD) support triggers adaptations within failing hearts. The HeartWare (HeartWare International, Inc., Framingham, MA) LVAD exhibits different flow profiles and afterload dependence compared with previous-generation devices, which may alter remodelling patterns. We sought to characterize myocardial adaptation to third-generation centrifugal-flow LVADs at a functional, hemodynamic, and structural level in addition to profiling transcriptomal changes using next-generation sequencing platforms. METHODS: We studied 37 patients supported with the HeartWare device with paired measurements of invasive hemodynamics, serial longitudinal left ventricular (LV) and right ventricular (RV) 3-dimensional echocardiography, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) measurements. Paired samples for comparison of histologic myocardial cellular size and transcriptomal profiling were performed on specimens taken at pump implant and transplantation. RESULTS: The mean support duration was 280 ± 163 days. Mechanical unloading after HeartWare support resulted in reduced filling pressures (mean pulmonary capillary wedge pressure 27.1 ± 6.6 to 14.8 ± 5.1 mm Hg, p < 0.0001). Mean LV cardiomyocyte cell size decreased from 2,789.7 ± 671.8 to 2,290.8 ± 494.2 µm2 (p = 0.02). LV and RV ejection fractions improved significantly (24% ± 8% to 35% ± 9% [p < 0.001] and 35% ± 11% to 40% ± 8% [p < 0.02], respectively). NT-proBNP levels fell 4.8-fold by Day 90 after support, consistent with a decrease in LV wall stress. Despite these concordant beneficial findings, the microRNA transcriptome did not change significantly across the group. CONCLUSIONS: Reverse remodelling is evident at multiple levels with chronic HeartWare support in the absence of changes in the microRNA transcriptome. Successful myocardial unloading is associated with a decrease in wall stress, regression of cardiomyocyte hypertrophy, and an improvement in LV and RV ejection fractions.

Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device Implantation or Heart Transplantation.

BACKGROUND: We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures. METHODS: Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried's Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx-including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention. RESULTS: Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention. CONCLUSIONS: Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.

The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.

BACKGROUND: Frailty is a clinically recognized syndrome of decreased physiological reserve. The heightened state of vulnerability in these patients confers a greater risk of adverse outcomes after even minor stressors. Our aim was to assess the prevalence and prognostic significance of the frailty phenotype in patients referred for heart transplantation. METHODS: Consecutive patients referred or on the waiting list for heart transplantation from March 2013 underwent frailty assessment. Frailty was defined as a positive response to 3 or more of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. In addition, markers of disease severity were obtained, and all patients underwent cognitive (Montreal Cognitive Assessment) and depression (Depression in Medical Illness-10) screening. RESULTS: One hundred twenty patients (83 men:37 women; age, 53 ± 12 years, range, 16-73 years; left ventricular ejection fraction, 27 ± 14%) underwent frailty assessment. Thirty-nine of 120 patients (33%) were assessed as frail. Frailty was associated with New York Heart Association class IV heart failure, lower body mass index, elevated intracardiac filling pressures, lower cardiac index, anemia, hypoalbuminemia, hyperbilirubinemia, cognitive impairment, and depression (all ρ < 0.05). Frailty was independent of age, sex, heart failure duration, left ventricular ejection fraction, or renal function. Frailty was an independent predictor of increased all-cause mortality: 1 year actuarial survival was 79 ± 5% in the nonfrail group compared with only 54 ± 9% for the frail group (P < 0.005). CONCLUSIONS: Frailty is prevalent among patients with advanced symptomatic heart failure referred for heart transplantation and is associated with increased mortality.

Cognitive impairment improves the predictive validity of physical frailty for mortality in patients with advanced heart failure referred for heart transplantation.

BACKGROUND: The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT). METHODS: Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes. RESULTS: Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality. CONCLUSIONS: The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death.