In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of ...patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation.
We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy.
Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute.
In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.
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.
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.
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).
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.
A severe shortage of available donor organs has created an impetus to use extended criteria organs for heart transplantation. Although such attempts increase donor organ availability, they may result ...in an adverse donor-recipient risk profile. The TransMedics Organ Care System (OCS) (TransMedics, Inc, Boston) allows preservation of the donor heart by perfusing the organ at 34°C in a beating state, potentially reducing the detrimental effect of cold storage and providing additional assessment options. We describe a single-center experience with the OCS in high-risk heart transplant procedures.
Thirty hearts were preserved using the OCS between February 2013 and January 2014, 26 of which (86.7%) were transplanted. Procedures were classified as high risk based on (1) donor factors, ie, transport time more than 2.5 hours with estimated ischemic time longer than 4 hours, left ventricular ejection fraction (LVEF) less than 50%, left ventricular hypertrophy (LVH), donor cardiac arrest, alcohol/drug abuse, coronary artery disease or (2) recipient factors, ie, mechanical circulatory support or elevated pulmonary vascular resistance (PVR), or both.
Donor and recipient age was 37 ± 12 years and 43 ± 13 years, respectively. Allograft cold ischemia time was 85 ± 17 minutes and OCS perfusion time was 284 ± 90 minutes. The median intensive care unit stay was 6 days. One death (3.8%) was observed over the follow-up: 257 ± 116 (109-445 days). There was preserved allograft function in 92% of patients, with a mean LVEF of 64% ± 5%.
Use of the OCS is associated with markedly improved short-term outcomes and transplant activity by allowing use of organs previously not considered suitable for transplantation or selection of higher risk recipients, or both.
Truncations of titin causing dilated cardiomyopathy Herman, Daniel S; Lam, Lien; Taylor, Matthew R G ...
New England journal of medicine/The New England journal of medicine,
02/2012, Letnik:
366, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Dilated cardiomyopathy and hypertrophic cardiomyopathy arise from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy ...mutations because of its enormous size.
We analyzed TTN in 312 subjects with dilated cardiomyopathy, 231 subjects with hypertrophic cardiomyopathy, and 249 controls by using next-generation or dideoxy sequencing. We evaluated deleterious variants for cosegregation in families and assessed clinical characteristics.
We identified 72 unique mutations (25 nonsense, 23 frameshift, 23 splicing, and 1 large tandem insertion) that altered full-length titin. Among subjects studied by means of next-generation sequencing, the frequency of TTN mutations was significantly higher among subjects with dilated cardiomyopathy (54 of 203 27%) than among subjects with hypertrophic cardiomyopathy (3 of 231 1%, P=3×10(-16)) or controls (7 of 249 3%, P=9×10(-14)). TTN mutations cosegregated with dilated cardiomyopathy in families (combined lod score, 11.1) with high (>95%) observed penetrance after the age of 40 years. Mutations associated with dilated cardiomyopathy were overrepresented in the titin A-band but were absent from the Z-disk and M-band regions of titin (P≤0.01 for all comparisons). Overall, the rates of cardiac outcomes were similar in subjects with and those without TTN mutations, but adverse events occurred earlier in male mutation carriers than in female carriers (P=4×10(-5)).
TTN truncating mutations are a common cause of dilated cardiomyopathy, occurring in approximately 25% of familial cases of idiopathic dilated cardiomyopathy and in 18% of sporadic cases. Incorporation of sequencing approaches that detect TTN truncations into genetic testing for dilated cardiomyopathy should substantially increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy. Defining the functional effects of TTN truncating mutations should improve our understanding of the pathophysiology of dilated cardiomyopathy. (Funded by the Howard Hughes Medical Institute and others.).
Aims
Patients treated with a Thoratec HeartMate II left ventricular assist device (LVAD) are supported at a fixed pump speed. It is uncertain whether pump speed has a significant effect on exercise ...capacity. We investigated the relationship between pump speed and exercise capacity and the influence of residual LV function
Methods and results
We exercised 30 patients 6 months after HeartMate II implantation at clinical pump speed (typically 9000 r.p.m.) and again at the lowest speed available (6000 r.p.m.). Overall, peak oxygen uptake (pkVO2) positively correlated with LV ejection fraction (LVEF) both at the clinical pump speed (r = 0.41, P = 0.03) and after pump speed reduction (r = 0.50, P = 0.01). We divided the patients into two groups; those with higher LVEF (LVEF ≥40%) and those with lower LVEF (LVEF <40%) at the time of exercise testing. The response to speed change was different between the two groups. In the higher LVEF group, the impact of LVAD pump speed reduction was minimal (pkVO2 21.4 ± 4.8 mL/kg/min vs. 20.8 ± 5.5 mL/kg/min, P = 0.38). In the lower LVEF group, the pkVO2 was lower at both speeds; 17.2 ± 5.3 and 14.7 ± 5.9 mL/kg/min, respectively. In the lower LVEF group, the pkVO2 decreased by 2.5 mL/kg/min (P = 0.02) with speed reduction.
Conclusions
HeartMate II patients with lower residual LV function had a lower pkVO2 and were more sensitive to pump speed reduction. This suggests that modulation of LVAD speed during exercise could be of benefit to this group of patients.
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.
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.
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.
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).
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.
Antibody-mediated rejection (AMR) is an important problem after heart transplantation. Most cases seem to occur in sensitized recipients with preformed donor-specific human leukocyte antigen antibody ...(DSA) early after transplantation. Few data exist on AMR in patients who form de novo DSA. We describe the clinical features and treatment outcome for late AMR secondary to de novo DSA.
This was a retrospective, observational cohort study. All heart transplant patients treated for symptomatic AMR secondary to de novo DSA between November 2005 and August 2011.
Fifteen patients were treated for AMR giving an incidence of 3.1 cases per 1000 person years and a prevalence of 1.4%. All had evidence of heart failure on presentation and de novo DSA at diagnosis. There was a spectrum of histologic and immunohistochemical findings. Despite treatment with immunepheresis, intravenous immunoglobulin, and rituximab, and in some cases total lymph node irradiation (n=3) and bortezomib (n=2), clinical outcomes were poor. DSA antibody levels, measured using Labscreen single antigen kits, were reduced by a mean of 76% with a median of 77% and a range of 35% to 99%, but were not eliminated. Forty-six percent had persistent cardiac allograft dysfunction. Mean and median survival was 1.3 and 0.8 years after diagnosis of AMR. Only 40% were alive at the end of the study period.
Late cardiac AMR caused by de novo DSA was an uncommon but serious problem. Despite treatment consistent with current best practice, 46% of patients developed persistent cardiac dysfunction and their medium-term survival was poor.
Ischemia time is a risk factor for mortality after heart transplantation that can be influenced by organizational factors such as transport arrangements and organ allocation.
We used the United ...Kingdom Cardiothoracic Transplant Audit database to analyze the outcome of 1491 first isolated orthotopic adult heart transplants performed between April 1995 and March 2004. Ischemia time and its components (transport time and surgical implant time) were related to 30-day mortality using a multivariable logistic regression model.
The median total ischemia time increased from 171 min (interquartile range: 149-198) to 213 min (interquartile range: 181-256) during the study period (P<0.0001). This was due to an increase in transport times that was partly explained by increased organ exchange between centers and also because of an increase in surgical implant times. Thirty-day survival decreased over the study period (91%-84%) with some evidence of a linear trend towards decreasing survival over time (P=0.089). After correcting for other known risk factors, the odds ratio of death within 30 days associated with each 15 min increment in transport time was 1.06 (95% confidence interval: 1.01-1.12) and with each 15 min increment in surgical implant time was 1.11 (95% confidence interval: 1.04-1.18).
Both transport and implant times were directly related to 30-day mortality after heart transplantation. Ischemia time should be considered in organ allocation and controlled during the heart transplant procedure.
PDF
