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Prolonged QT and cardiac arrest after heart transplantation: Inherited or acquired?
... So far, only one case of unplanned but successful "LQTS heart" transplantation with subsequent ICD implantation has been reported [2] . According to our knowledge it was not confirmed by genetic studies. ...
Introduction:
Brugada syndrome is an inherited channelopathy characterized by arrhythmia and an increased risk of sudden cardiac death (SCD). Implantation of a defibrillator for primary or secondary prevention is the only effective strategy to decrease the risk of SCD in Brugada syndrome. We present a case in which a cardiac donor had a pathogenic variant for Brugada syndrome, discovered on genetic testing after transplantation.
Case report:
A young child with dilated cardiomyopathy underwent orthotopic heart transplantation from a donor with in-hospital cardiac arrest in the context of fever and a normal ECG. Approximately 1 month after transplant, the donor's post mortem genetic testing revealed a pathogenic loss-of-function SCN5A variant associated with Brugada syndrome, which was confirmed on genetic testing on a post-transplant endomyocardial biopsy from the recipient. The recipient's post-transplant electrocardiographic monitoring revealed persistent right bundle branch block and progressive, asymptomatic sinus node dysfunction. The recipient was managed with precautionary measures including aggressive fever management, avoidance of drugs that increase arrhythmia risk in Brugada syndrome, and increased frequency of arrhythmia surveillance. The recipient remains asymptomatic at over 3 years post-transplant with preserved graft function and no documented ventricular arrhythmias.
Conclusion:
We describe the clinical course of "acquired" Brugada syndrome in a cardiac allograft recipient, which has not been previously reported. The time-sensitive nature of donor organ selection, especially in critically ill recipients, combined with the growing use of molecular autopsies in patients with unexplained etiologies for death may increasingly result in important donor genetic information being made available after transplantation.
Background:
Assessing the QT interval in donors is important to exclude long QT syndrome as the cause of death. A donor heart with a corrected QT (QTc)>500 msec is often concerning. We sought to evaluate first-year outcomes for donors with a QTc interval > 500 msec.
Methods:
Between 2010 and 2014, we assessed 257 donor hearts for QTc interval > 500msec. Post-transplant outcomes included 1-year survival, 1-year freedom from any-treated rejection, 1- year freedom from CAV defined as stenosis ≥ 30% by angiography, and 1-year freedom from Non-Fatal Major Adverse Cardiac Events.
Results:
Patients with QTc interval > 500 msec had a significantly lower 1-year freedom from CAV development. There were no significant differences for other outcomes. A significantly higher percentage of donors with QTc > 500 msec had a stroke or subarachnoid hemorrhage. Multivariate analysis found that donor QTc > 500 msec was associated with a 6.7-fold increased risk of developing CAV (p=0.029, 95% CI 1.21-36.6) after adjusting for other known risk factors.
Conclusion:
QTc > 500 msec in the donor heart appears to be an independent risk factor for the development of early CAV after heart transplantation possibly due to a higher immunological risk. This article is protected by copyright. All rights reserved.
Background
Currently a shortage of donor lungs remains the most important limitation to lung transplantation. Short-term and long-term effects of lung transplants with extended donors are not well known. This study evaluated the outcome of recipients of lungs from extended donors in our program.
Methods
We performed a retrospective analysis of 492 consecutive lung transplants at our institution from January 2007 through September 2012. Recipients were divided into two groups, standard donor (SD) or extended donor (ED). ED was defined as having one of the following criteria: donor age> 55 years, pulmonary contusion, pulmonary inflammation, smoking 20 pack/year, duration of ventilation longer than 5 days, purulent secretions or inflammation at bronchoscopy, PO2 < 300 on FiO2 100%, Chest X-ray/ CT indicate infiltration, Localized emphysema. The primary end point was 30-day, 6-month and 12-month mortality. Survival data were calculated by Kaplan-Meier analysis with the Log-Rank test.
Results
Of 492 double/single lung transplants done, 156(31.7 %) were from ED. The two groups were evenly matched in recipient age, sex and BMI. ED group had 62 elderly donors (mean 59.3 years old, range 55-70); 50 smokers; 51 intubation>5 days; 26 all others. Primary diagnoses and double or single lung transplant were not significantly different between two groups. The 30-day mortality for SD was 18(5.4%) of 336 versus 16(10.3 %) of 156 for ED (P=0.049). The six-month mortality for SD was 37(11%) of 336 versus 32(20.5%) of 156 for ED (P=0.018). The 12-month mortality for SD was 49(14.6%) of 336 versus 37 (23.7 %) of 156 for ED. The 30-day, 6-month and 12-month mortality for SD versus ED if smoker lungs were excluded was not statistically significant (p=0.42, 0.067, 0.11).
Conclusions
The result of this analysis showed inferior outcomes from ED with heavy smoking history. Donor age > 55 years, intubation time and mild lung contusion had no significant effect on postoperative survival.
Introduction and Background: Gross disparity between organ demand
and supply created a profound negative impact on organ transplantation.
Organ supply system depends on altruistic non-coercive
donation (ADS). Desperate demand for organs and the need to combat
organ trafficking, transplant tourism and human exploitation have
resulted in the search for effective alternatives. Financial incentives
are one of them. Its feasibility is debatable as it relates to medical, ethical
and economic dimensions.
In Riyadh, Saudi Arabia, organ shortage was approach by Incentivebased
procurement system (IBPS) applied by Mobile Donor Action
Team (MDAT). Aggressive approach towards incentives for donors'
families and health workers was associated with a threefold increase
in donation rate.
The aim is to provide a qualitative review of a five-year IBPS and to assess
medical, ethical, religious, cultural and economic issues that
have, and may impact the system and to make recommendations to
the transplant community and health authority in KSA and elsewhere
regarding the transferability of the system and areas for further
research.
Method Is qualitative. Review of documents was used to create a chronological
audit and to shape interviewquestions. Samplingwas purposeful and inclusive
of MDAT members. Semi-structured interviews were conducted. Findings
were subjected to thematic analysis.
Result Documents reflected evolution of MDAT. The essence of MDAT is
field work and liberal use of financial incentive resulting in 3 fold increase in
donation rate. MDAT members believed that IBPS is the reason behind this
increase. Moreover, IBPS has been acceptable from moral, ethical and religious
aspects with high degree of professional satisfaction.
Discussion Theoretical assumptions doubted the feasibility of IBPS. This
real-life experience with IBPS proved the contrary. The findings may be applicable
only to the setting in Riyadh, KSA. Further research is needed to
explore its transferability to other settings.
Conclusion IBPS can be an alternative to ADS and should be piloted in
different settings.
Background and Aim: Cadaveric organ donation started in 1986, out
of 8820 cases reported, 4661 cases documented, and 1384 donors
harvested since the program inception until the end of 2011, with conversion
rate of 29.7%. There is marked regional variation in organ donation
among different region of Saudi Arabia. Our aim is to study the
reasons for this variation in order to improve organ donation in areas
of low donation rate.
Method: Saudi Center for organ transplantation (SCOT) data for cadaveric
organ donation from 2006–2011 detailing the number of cases
reported, documented, consented and harvested, as well as the distribution
by region (central 29.4% of the total population Saudi Arabia,
western 32%, eastern 15%, northern 8%, southern 15.6%). The number
of contributing ICU stratified by size of ICU and the region was
also reviewed.
The overall donation rate as well as the percentage of harvested cases
per region as well as the conversion rate (harvested/Documented)
was reviewed.
Results: Between 2006–2011, 448 cases procured form Saudi Arabia,
of which 343 where procured for central region representing 76.5%
coming from 30 out of 97 contributing ICU's (31%), the eastern region
came second with 49 cases (11%) followed by the western region with
35 cases (7.8%) while northern and southern region had 12 and 9 cases
(2.7&2%) respectively. The conversion rate followed a similar trend.
This is related to the presence of active mobile donor team in Riyadh
(the capital) as well as active transplant centers.
Conclusion: There is marked variation with regards of contribution to
organ donation in different regions in Saudi Arabia from 2% in the
southern area to 76.5% in central area. This is related to the presence
of active mobile donor team in the central region. A similar trend towards
increasing number of cases and conversion rate was observed
in the eastern region after having a new mobile donor team. We suggest
that having active well trained mobile donor team in each region
will increase the number of cadaveric donor at least 3 folds in the next
3–5 years.
Keywords: Cadaveric organ donation, Regional variation, Donor team
King Faisal Liver Group
November 27, 2013
S246 Supplement
Background: Living donor liver transplantation has the advantage of
avoiding the long waiting time for cadaveric liver transplantation with
possibility of decreasing mortality before liver transplantation.
Objective: To identify the mortality in patients with decompensated
cirrhosis with potential living donor during the evaluation process for
both donors and recipients before liver transplantation.
Methods: We retrospectively reviewed our records for patients with
liver cirrhosis requiring liver transplantation that has a potential donor,
the number of donors evaluated for each candidate, the mortality during
the evaluation process either related to complication of liver disease
or progression of hepatocellular carcinoma (HCC).
Results: Out of 370 liver cirrhosis patients with potential living donor
for liver transplantation, 102 died (27.6%), 79 died related to complication
of liver disease and 23 related to HCC progression.
The mortality increased as the number of donors evaluated increase,
it was 27.6% for patients with one or two donors (86 out of4=311),
37% for patients with 3 donors evaluated (13 out of 35), and 50% with
five or seven donors evaluated (2 out of 4). We do not have a MELD
limit for living donor and patients with MELD >25 are discussed in
case to case bases, and the donor work up time from 2 to 18 days (average
10 days).
Conclusion: The mortality is high in patients with potential living donor
liver transplantation, with increase in mortality as the number of
potential donors increase.
This may be explained by the time needed for the donor evaluation as
well as late referral.
King Faisal Liver Group
Objectives. The objectives of this study were to determine whether a signal-averaged electrocardiogram (SAECG) or measurement of interlead variability of QT intervals on an electrocardiogram (ECG) obtained at the time of wait-listing could provide prognostic value with respect to cardiac death during the waiting period.Background. Because heart transplantation is a life-saving but limited resource, there remains an urgent need to identify those patients at greatest risk of dying while awaiting heart transplantation as part of the strategy to optimize the allocation of donor organs to those in greatest need. This study was undertaken to prospectively identify clinical, ECG or SAECG variables that might predict mortality during the waiting period.Methods. Of 108 consecutive patients referred for heart transplant evaluation, 80 were placed on a waiting list, at which time a standard 12-lead ECG and a SAECG were recorded. In this cohort of 80 patients, QT dispersion was characterized from the 12-lead ECG as either the maximal–minimal QT interval (QTDISP) or as the coefficient of variation of all QT intervals (QTCV).Results. During the 25-month follow-up period (mean time on waiting list, 201 days), the mortality rate was 27%/year, divided equally between heart failure and sudden deaths. No clinical variable identified at entry predicted mortality. QTDISP and QTCV were strong mortality predictors, with a 4.1-fold increase in mortality in patients with QTDISP >140 ms compared with those patients with QTDISP ≤140 ms (95% CI 1.1 to 14.9), whereas a QTCV ≥9% also predicted a 4.1-fold increased risk of death (95% CI 1.4 to 11.8). Although 88% of all SAECGs were abnormal, no patient with a normal SAECG died suddenly during the waiting period.Conclusions. Indexes of QT dispersion provide a means of stratifying a patient’s risk of dying while awaiting heart transplantation and may help to establish priority on a heart transplant waiting list.(J Am Coll Cardiol 1997;29:1576–84)
Currently, endomyocardial biopsy is the most reliable method to detect an acute rejection after heart transplantation. However, as an invasive procedure it is associated with a definite risk for complications. Therefore, it was examined whether changes in QT time and QT dispersion on the surface ECG are able to predict an acute cellular rejection.
During the first 3 months after heart transplantation, QT time, heart rate-corrected QT time (QTc time), QT dispersion, and heart rate-corrected QT dispersion (QTc dispersion) were analyzed in 100 patients with acute cellular rejection grade > or = II according to the International Society for Heart and Lung Transplantation (ZA group), and in 100 patients without or with only mild rejection episodes (< or = grade I; MA group). Results were obtained by determining the difference in the ZA group between the QT interval in the presence of a rejection and the QT interval at other time points, which were then compared with the results of the MA group at matched time points.
At the time point of rejection, the ZA group showed a mean prolongation in both QTc time and QTc dispersion of > 40 ms compared with other time points. Such differences were not seen in the MA group (p < 0.001 for comparisons between study groups). If prolongations in QTc time and QTc dispersion of > 25 ms were used as predictors for an acute rejection, sensitivity was 77% and 70%, respectively, and specificity was 96% and 95%, respectively.
Provided that ECGs are performed regularly, measurements of QTc time and QTc dispersion can reliably be used to detect an acute rejection in the early phase after heart transplantation.
The hereditary long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity to syncope, polymorphous ventricular tachycardia (torsades de pointes), and sudden arrhythmic death. This inherited cardiac disorder constitutes an important cause of malignant ventricular arrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. Risk assessment in affected LQTS patients relies upon a constellation of electrocardiographic, clinical, and genetic factors. Administration of beta-blockers is the mainstay therapy in affected patients, and primary prevention with an implantable cardioverter defibrillator or left cervicothoracic sympathetic denervation are therapeutic options in patients who remain symptomatic despite beta-blocker therapy. Accumulating data from the International LQTS Registry have recently facilitated a comprehensive analysis of risk factors for aborted cardiac arrest or sudden cardiac death in pre-specified age groups, including the childhood, adolescence, adulthood, and post-40 periods. These analyses have consistently indicated that the phenotypic expression of LQTS is time dependent and age specific, warranting continuous risk assessment in affected patients. Furthermore, the biophysical function, type, and location of the ion-channel mutation are currently emerging as important determinants of outcome in genotyped patients. These new data may be used to improve risk stratification and for the development of gene-specific therapies that may reduce the risk of life-threatening cardiac events in patients with this inherited cardiac disorder.
Hintergrund und Ziel: Die endomyokardiale Biopsie stellt zurzeit noch die zuverlässigste Methode zur Detektion akuter Abstoßungen nach Herztransplantation dar. Sie ist als invasive Prozedur jedoch mit einem nicht unbedeutenden Komplikationsrisiko behaftet. In der vorliegenden Studie wurde untersucht, ob Veränderungen der QT-Zeit sowie der QT-Dispersion im Oberflächen-EKG geeignet sind, eine akute zelluläre Abstoßung vorauszusagen. Patienten und Methodik: Bei 100 Patienten mit akuter Abstoßungsreaktion vom Grad II gemäß Klassifikation der International Society for Heart and Lung Transplantation oder höher (ZA-Gruppe) sowie bei 100 Patienten ohne Abstoßung bzw. mit lediglich einer milden Abstoßungsreaktion (≤ Grad I; MA-Gruppe) wurden QT-Zeit, herzfrequenzkorrigierte QT-Zeit (QTc-Zeit), QT-Dispersion und herzfrequenzkorrigierte QT-Dispersion (QTc-Dispersion) in den ersten 3 Monaten nach Herztransplantation analysiert. Die Auswertung erfolgte, indem in der ZA-Gruppe die Differenz zwischen der QT-Strecke zum Zeitpunkt der Abstoßung und verschiedenen anderen Untersuchungszeitpunkten gebildet und anschließend mit den zu identischen Zeitpunkten erhobenen Daten der MA-Gruppe verglichen wurde. Ergebnisse: Die ZA-Gruppe wies während der Abstoßung im Mittel eine Verlängerung von QTc-Zeit und QTc-Dispersion > 40 ms gegenüber den anderen Untersuchungszeitpunkten auf. Derartige Veränderungen traten in der MA-Gruppe nicht auf (Unterschiede zwischen den beiden Gruppen jeweils p Schlussfolgerung: Die Ermittlung von QTc-Zeit und -Dispersion kann unter der Voraussetzung, dass regelmäßige EKG-Bestimmungen durchgeführt werden, als vertrauenswürdige Methode zur Erfassung akuter kardialer Abstoßungsreaktionen in der Frühphase nach Herztransplantation eingesetzt werden kann.
Thanks to the contribution of molecular genetics, the genetic bases, the pathogenesis and genotype-phenotype correlation of diseases such as the long QT syndrome and catecholaminergic polymorphic ventricular tachycardia have been progressively unveiled and show an extremely high degree of genetic heterogeneity. Data from clinical registries are summarized together with the recommendations provided in clinical practice guidelines for management of patients with these diseases. Furthermore the evidence supporting the importance of genetic analysis for risk stratification and therapy selections is reviewed.
Heart donor candidates have severe neurologic injuries that have been associated with significant prolongation of the corrected QT (QTc) interval. Screening for an underlying abnormality of cardiac repolarization such as the long-QT syndrome thus becomes difficult. The aims of this study were to establish normal values and determine factors associated with prolongation of pre- and post-transplantation QTc intervals in a large cohort of heart transplantation donors and recipients. The medical records of 179 donors and 112 recipients were reviewed for historical, electrocardiographic, and neuroimaging data. After linear regression analysis, gunshot wounds were associated with the shortest mean pre-transplantation QTc interval of 447 +/- 51 ms (p = 0.016), whereas all other mechanisms of brain injury were associated with markedly prolonged QTc intervals. Overall, the mean QTc interval decreased from 467 +/- 58 to 446 +/- 47 ms (p <0.001), the mean QRS duration increased from 87 +/- 16 to 98 +/- 21 ms (p <0.001), and the mean QT dispersion did not change significantly after transplantation. The only factor associated with a prolonged QTc interval in the post-transplantation period was hypokalemia, with a mean QTc of 468 +/- 37 ms (p = 0.047). In conclusion, the mechanism of donor brain injury is associated with alterations in the pre-transplantation QTc interval, with the shortest intervals related to gunshot wounds. Fewer than 5% of the donor population was found to have QTc interval > or =580 ms. For those afflicted by gunshot wounds, <5% had QTc intervals > or =550 ms. This information can be used in pre-transplantation donor assessment, and post-transplantation management can be tailored to avoid the occurrence of ventricular arrhythmia.
Ventricular fibrillation (VF) is the primary mechanism of cardiac arrest in the vast majority of sudden death patients. Whether similar modes and mechanisms of death can be generalized to denervated hearts in orthotopic heart transplantation (OHT) patients is unknown.
The purpose of this study was to determine the mode and mechanisms of death in patients who have undergone cardiac transplantation.
We analyzed the outcomes of 628 patients who underwent OHT between January 1994 and December 2004. The mode of death was classified as either sudden death (SD) or non-sudden death (NSD). The first documented rhythm taken at the time of arrest was also reviewed to determine the mechanism of cardiac arrest.
During a mean follow-up of 76 months, 194 patients died. Of these, the mode of death could be determined in 116 patients (60%). Forty-one patients (35%) died of SD, and 75 patients (65%) died of NSD. The first documented rhythm of death was available in 91 patients (26 SD and 65 NSD). The terminal rhythms in patients who died suddenly were: asystole (34%), pulseless electrical activity (PEA) (20%), and VF (10%). In NSD patients, the terminal rhythms were asystole (73%), followed by VF (7%), and PEA (7%), P < .001 compared with SD patients.
SD represented the mode of death in 35% of OHT patients. The main mechanisms underlying SD in this population were asystole and PEA, suggesting that denervation of the donor heart, among other post-transplantation changes, may alter susceptibility to VF.
This Seminar presents the most recent information about the congenital long and short QT syndromes, emphasising the varied genotype-phenotype association in the ten different long QT syndromes and the five different short QT syndromes. Although uncommon, these syndromes serve as a Rosetta stone for the understanding of inherited ion-channel disorders leading to life-threatening cardiac arrhythmias. Ionic abnormal changes mainly affecting K(+), Na(+), or Ca(2+) currents, which either prolong or shorten ventricular repolarisation, can create a substrate of electrophysiological heterogeneity that predisposes to the development of ventricular tachyarrhythmias and sudden death. The understanding of the genetic basis of the syndromes is hoped to lead to genetic therapy that can restore repolarisation. Presently, symptomatic individuals are generally best treated with an implantable cardioverter defibrillator. Clinicians should be aware of these syndromes and realise that drugs, ischaemia, exercise, and emotions can precipitate sudden death in susceptible individuals.
The objectives of this study were to determine whether a signal-averaged electrocardiogram (SAECG) or measurement of interlead variability of QT intervals on an electrocardiogram (ECG) obtained at the time of wait-listing could provide prognostic value with respect to cardiac death during the waiting period.
Because heart transplantation is a life-saving but limited resource, there remains an urgent need to identify those patients at greatest risk of dying while awaiting heart transplantation as part of the strategy to optimize the allocation of donor organs to those in greatest need. This study was undertaken to prospectively identify clinical, ECG or SAECG variables that might predict mortality during the waiting period.
Of 108 consecutive patients referred for heart transplant evaluation, 80 were placed on a waiting list, at which time a standard 12-lead ECG and a SAECG were recorded. In this cohort of 80 patients, QT dispersion was characterized from the 12-lead ECG as either the maximal-minimal QT interval (QTDISP) or as the coefficient of variation of all QT intervals (QTCV).
During the 25-month follow-up period (mean time on waiting list, 201 days), the mortality rate was 27%/year, divided equally between heart failure and sudden deaths. No clinical variable identified at entry predicted mortality. QTDISP and QTCV were strong mortality predictors, with a 4.1-fold increase in mortality in patients with QTDISP > 140 ms compared with those patients with QTDISP < or = 140 ms (95% CI 1.1 to 14.9), whereas a QTCV > or = 9% also predicted a 4.1-fold increased risk of death (95% CI 1.4 to 11.8). Although 88% of all SAECGs were abnormal, no patient with a normal SAECG died suddenly during the waiting period.
Indexes of QT dispersion provide a means of stratifying a patient's risk of dying while awaiting heart transplantation and may help to establish priority on a heart transplant waiting list.
Although QTc interval prolongation is considered a risk factor for adverse outcome in the non-transplant population, its predictive value in heart transplant recipients has not been studied yet. This study was conducted to determine whether prolonged QTc interval is a useful predictor of outcome in heart transplant recipients.
QTc intervals were measured in 587 adult patients who underwent heart transplantation between May 1982 and January 2002. QT interval duration was determined by averaging 3 consecutive beats in all 12 leads of the standard electrocardiogram (ECG) and corrected with the Bazett formula. Baseline ECGs were obtained within 7 days after transplantation; follow-up ECGs were recorded annually at the time of routine angiography. Patients were followed over 85 +/- 65 months (range, 3 months-17 years).
During follow-up, 241 patients died. The mean QTc interval duration in these patients was comparable with that in the remaining cohort (432 +/- 26 msec vs 423 +/- 25 msec, p = 0.07). However, patients with a relative increase in QTc duration of >or=10% between the first and second post-transplantation year (DeltaQTc >or= 10%) had a 6.86-times higher risk of dying compared with patients with DeltaQTc < 10% (p = 0.0005). Furthermore, DeltaQTc >or= 10% was the only independent predictor of long-term mortality on multivariate analysis (p = 0.0008).
A relative increase in QTc interval duration of >or=10% between the first and second post-transplantation year is a strong, independent predictor of mortality in heart transplant recipients.