Specialization in Acute Type A Aortic Dissection Repair: The Outcomes and Challenges.

With increasing specialization within the field of cardiac surgery and a positive relationship between case volume and surgical outcomes in many areas, the concept of dedicated aortic surgeons performing acute type A aortic dissection (ATAAD) repair was investigated. From 1996 to 2014, 436 patients underwent open surgical repair of an ATAAD and were subsequently divided based on surgeon subspecialization, aortic-surgeon (AS, n = 401) vs non-aortic-surgeon (NAS, n = 35). Each aortic surgeon performed an average of 13 ATAAD repair operations per year. Preoperative comorbidities were similar between groups. Intraoperatively, the AS group had 36% aortic root replacement vs 23% in the NAS group, P = 0.12, and 36% zone 1/2/3 arch replacement vs 26% in the NAS group, P = 0.20). Postoperatively, the AS group had significantly better outcomes, including intraoperative mortality (1.2% vs 5.7%), 30-day mortality (6.5% vs 17%), and composite outcomes (23% vs 46%). Multivariable logistic regression showed NAS was a risk factor for 30-day mortality with an odds ratio (OR) of 4.4 (P = 0.03), as were COPD (OR = 4.0, P = 0.046) and cardiogenic shock (OR = 13.4, P < 0.0001). The 10-year survival was 66% in the AS group vs 46% in the NAS group, P = 0.02. NAS (HR = 2.2), Age (hazard ratio (HR) = 1.05), COPD (HR = 1.96), acute stroke (HR = 3.0), and New York Heart Association class III or IV (HR = 1.75) were significant risk factors for long-term mortality. Managing ATAAD by subspecialized aortic surgeons resulted in improved short- and long-term outcomes. Our specialty could consider ATAAD repair by high-volume aortic surgeons for better patient outcomes.

Stentless Versus Stented Aortic Valve Replacement for Aortic Stenosis.

BACKGROUND: The differences in long-term outcomes of aortic valve replacement for aortic stenosis between stentless and stented bioprostheses are controversial. METHODS: Between 2007 and 2018, 1173 patients underwent aortic valve replacement for aortic stenosis, including 559 treated with a stentless valve and 614 with a stented valve. A propensity score matched cohort with 348 pairs was generated by matching for age, sex, body surface area, bicuspid aortic valve, chronic lung disease, previous cardiac surgery, coronary artery disease, renal failure on dialysis, valve size, concomitant procedures, and surgeon. The primary endpoints of the study were long-term survival and incidence of reoperation. RESULTS: Immediate postoperative outcomes were similar between the stentless and stented groups with an overall operative mortality of 2.9% (P = .19). Kaplan-Meier estimation for long-term survival was comparable between the stentless and stented valves in both the whole cohort and the propensity score matched cohort (10-year survival 59% vs 55%, P = .20). The hazard ratio of stentless vs stented valve for risk of long-term mortality was 1.12 (P = .33). The 10-year cumulative incidence of reoperation due to valve degeneration was 5.5% in the stentless group and 4.7% in the stented group (P = .25). The transvalvular pressure gradient at 5-year follow-up was significantly lower in the stentless group (7 vs 11 mm Hg, P < .001). CONCLUSIONS: Both stented and stentless valves could be used in aortic valve replacement for aortic stenosis. We recommend stented valves for aortic valve replacement in patients with aortic stenosis for their simplicity of implantation.

Quality of Life Worsens After Surgical Repair of Acute Type A Aortic Dissection.

This study aimed to determine how acute type A aortic dissection (ATAAD) impacts patients' quality of life. The 36-Item Short Form Survey (SF-36) was used to measure quality of life. The eight SF-36 scales were aggregated into a two-factor summary: physical and mental component summary scales (PCS and MCS). One hundred fourteen patients were included in the ATAAD group and 81 patients in the aortic valve replacement (AVR) group. All patients underwent surgery between June 2007 and December 2018. Surveys were completed after the operation. The mean scaled score of the ATAAD group decreased significantly in all eight domains of the SF-36 survey after aortic dissection repair except mental health. Also, the postsurgery PCS score was significantly lower than the presurgery score (39 vs 49; P < 0.0001). Multivariable regression confirmed the negative impact of ATAAD on postsurgery PCS score and higher presurgery PCS score had a significant positive impact. The postsurgery MCS score did not change significantly (49 vs 50; P = 0.32), but higher preoperative MCS score had a significant positive impact on the postsurgery MCS score. Age, sex, connective tissue disorders, and stroke did not contribute significantly to the postsurgery PCS and MCS scores. The AVR group had significantly increased postsurgery PCS and MCS scores compared to the presurgery scores (47 vs 41; P < 0.0001) and (53 vs 51; P = 0.02) respectively. Patients reported significantly decreased physical health after recovery from acute type A aortic dissection repair. A multidisciplinary approach is needed to improve patients' quality of life.

Managing Malperfusion Syndrome in Acute Type A Aortic Dissection With Previous Cardiac Surgery.

BACKGROUND: Patients with acute type A aortic dissection with a previous cardiac surgery (PCS) and malperfusion syndrome (MPS) are extremely difficult to manage and have poor outcomes. METHODS: From 1996 to 2018, 668 patients underwent emergent open aortic repair or endovascular fenestration/stenting for MPS for an acute type A aortic dissection, including those with PCS (PCS, n = 64) and those without PCS (No-PCS, n = 604). The groups were further divided into PCS+MPS, PCS+No-MPS, No-PCS+MPS, and No-PCS+No-MPS. RESULTS: Compared with the No-PCS group, the PCS group had significantly more coronary artery disease, acute renal failure, and mesenteric and renal MPS. Forty-two percent of patients with PCS underwent upfront endovascular fenestration/stenting for endovascular-amendable MPS. The in-hospital mortality was significantly higher in patients with PCS+MPS (40%) compared with PCS+No-MPS (5.9%), No-PCS+MPS (30%), and No-PCS+No-MPS (6.7%). Multivariable logistic regression showed cardiogenic shock (odds ratio, 7.3) and MPS (odds ratio, 6.6) were risk factors for in-hospital mortality (P < .001). After recovering from MPS the PCS group (n = 54) had similar rates of postoperative complications, including 30-day mortality (7.4% vs 6.3%, P = .77), compared with the No-PCS group (n = 557). The 5-year survival was significantly lower in the PCS group compared with the No-PCS group (60% vs 72%, P = .004) and was lowest in those with PCS+MPS (46%). PCS was not a significant risk factor for in-hospital (odds ratio, 1.2; P = .63) or late (hazard ratio, 1.3; P = .27) mortality. CONCLUSIONS: Because of severe preoperative comorbidities and the complexity of open aortic repair, in acute type A aortic dissection patients with PCS and MPS, endovascular fenestration and stenting first with delayed redo sternotomy and central aortic repair was a valid approach.

Root abscess in the setting of infectious endocarditis: Short- and long-term outcomes.

OBJECTIVES: To evaluate the influence of an aortic root abscess on perioperative outcomes and long-term survival in patients with active infectious endocarditis that was treated surgically. METHODS: From 1996 to 2017, 336 consecutive patients were treated with aortic valve or root replacement for infective endocarditis, including patients with (n = 179) or without (n = 157) a root abscess. Data were obtained from the Society of Thoracic Surgeons data warehouse, through chart review, patient surveys, and National Death Index data. RESULTS: Demographic characteristics were similar between groups except the root abscess group had a significantly lower prevalence of congestive heart failure and higher rates of prosthetic valve endocarditis. The abscess group had significantly more aortic root replacements as well as longer cardiopulmonary bypass and crossclamp times. Operative mortality was 8.4% and 3.8% (P = .11) for the abscess and no abscess groups, respectively. Nevertheless, the root-abscess group had prolonged ventilation and longer intensive care unit stays. Kaplan-Meier survival was similar between root abscess and no abscess groups (10-year survival 41% vs 43%; P = .35). Significant risk factors for all-time mortality included age greater than 70 (hazard ratio [HR], 2.85; 95% confidence interval [CI], 1.55, 5.24), the presence of a root abscess (HR, 1.42; 95% CI, 1.02, 1.96), intravenous drug use (HR, 1.81; 95% CI, 1.13, 2.89), congestive heart failure (HR, 1.72; 95% CI, 1.22, 2.42), renal failure requiring dialysis (HR, 3.26; 95% CI, 2.30, 4.64), liver disease (HR, 3.04; 95% CI, 1.65, 5.60), and postoperative sepsis (HR, 3.00; 95% CI, 1.30, 6.93). The 10-year rate of reoperation was also similar between groups (5.9% vs 7.9%). CONCLUSIONS: Thorough and extensive debridement is critical for successful treatment of active endocarditis with root abscess. Bioprosthetic stented and stentless valves are valid conduits to treat endocarditis with root abscess.

Aortic Valve Endocarditis with Anomalous Origin of the Right Coronary Artery and Unknown Infected Thrombus in the Dissected Descending Thoracic Aorta.

We report an intricate aortic root replacement in a young male patient suffering from native valve infective endocarditis due to Serratia marcescens. Further complicating the total root replacement, there was an unknown infected aortic thrombus and a concomitant anomalous right coronary artery with an intramural course. As a result of our more aggressive approach, we believe that we lowered the risk of recurrent infection of the bioprosthesis of the aortic root.

Higher admission rates and in-hospital mortality for acute type A aortic dissection during Influenza season: a single center experience.

Triggering events for acute aortic dissections are incompletely understood. We sought to investigate whether there is an association between admission for acute type A aortic dissection (ATAAD) to the University of Michigan Medical Center and the reported annual influenza activity by the Michigan Department of Health and Human Services. From 1996-2019 we had 758 patients admitted for ATAAD with 3.1 admissions per month during November-March and 2.5 admissions per month during April-October (p = 0.01). Influenza reporting data by the Michigan Department of Health and Human Services became available in 2009. ATAAD admissions for the period 2009-2019 (n = 455) were 4.8 cases/month during peak influenza months compared to 3.5 cases/month during non-peak influenza months (p = 0.001). ATAAD patients admitted during influenza season had increased in-hospital mortality (11.0% vs. 5.8%, p = 0.024) and increased 30-day mortality (9.7 vs. 5.4%, p = 0.048). The results point to higher admission rates for ATAAD during months with above average influenza rates. Future studies need to investigate whether influenza virus infection affects susceptibility for aortic dissection, and whether this risk can be attenuated with the annual influenza vaccine in this patient population.

Cryoablation of Intercostal Nerves Decreased Narcotic Usage After Thoracic or Thoracoabdominal Aortic Aneurysm Repair.

To improve surgical pain control through cryoablation of intercostal nerves and reduce narcotic usage in patients undergoing open thoracic or thoracoabdominal aortic aneurysm (TAA or TAAA) repair. From 2012 to 2018, 117 patients underwent open repair of TAA or TAAA. Of those patients, 25 (21%) received cryoablation (2016-2018) of their intercostal nerves and 92 (79%) did not (2012-2018). The primary outcome was pain scores and narcotic usage from extubation day 1 to 10 or the day of discharge. The median age (57 years), demographics, and preoperative comorbidities were not significantly different between the 2 groups. The cryoablation group had significantly more incidences of thoracoabdominal incisions (52% vs 28%), urgent operations (32% vs 11%), and longer duration of chest tubes compared to the noncryoablation group (all P < 0.05). T9-T12 intercostal arteries were selectively reimplanted. Left intercostal nerves were cryoablated from T3 to T9 if 2 thoracotomies were used; or 2 intercostal spaces above and below the thoracotomy if 1 thoracotomy was used. There were no significant differences between the noncryoablation and cryoablation groups in postoperative stroke, paraplegia (5%), pneumonia, and in-hospital mortality (0.9%). However, the average usage of narcotics was significantly reduced in the cryoablation group by 28 measured morphine equivalents (equal to four 5 mg Oxycodone)/patient/day in 10 days after extubation, P = 0.005. With cryoablation of intercostal nerves, the postoperative surgical pain was well controlled and narcotic usage was significantly decreased after TAA or TAAA repair. Cryoablation of intercostal nerves was a safe and effective measure for postoperative pain control in TAA or TAAA repair.

A Novel Variant in APOB Gene Causes Extremely Low LDL-C Without Known Adverse Effects.

A novel frameshift variant was identified in APOB that segregates in a dominant manner with low levels of low-density lipoprotein cholesterol. Affected family members show no apparent clinical complications. There is no consensus regarding clinical management, and the long-term consequences of low levels of low-density lipoprotein cholesterol remain unknown. (Level of Difficulty: Advanced.).

Management of Ruptured Left Ventricular Outflow Tract.

Left ventricular outflow tract pseudoaneurysm is a potentially fatal complication after aortic root replacement. Challenges surrounding multiple reoperations on the aortic root include sternal reentry, bleeding, valve positioning, compression of coronary arteries, and navigating concomitant interventions. We present a 27-year-old patient with mechanical valves in the aortic and mitral positions and a left main coronary artery drug-eluting stent for left main compression after being diagnosed with rheumatic heart disease at age 16. She underwent a fourth redo modified Bentall procedure with a homemade mechanical composite graft for the contained rupture of an left ventricular outflow tract pseudoaneurysm.

Dissection of Arch Branches Alone: An Indication for Aggressive Arch Management in Type A Dissection?

BACKGROUND: It is controversial if extension of aortic dissection into arch branches should be an indication for replacement of the arch and its branches in acute type A aortic dissection. METHODS: From 2008 to April 2018, 399 patients underwent open repair for an acute type A aortic dissection, and 190 patients had known innominate and/or left common carotid artery dissection without malperfusion syndrome, including no arch procedure (n = 1)/hemiarch replacement (n = 109) and zone 1/2/3 arch replacement (n = 80) with replacement of 1 to 4 arch branch vessels. RESULTS: Median patient age was 58 years. Preoperative comorbidities were similar between groups, except the hemiarch group had more coronary artery disease (22% vs 3%, P = .0002). Both groups underwent similar aortic root procedures and other concomitant procedures with equivalent cardiopulmonary bypass and aortic cross-clamp times. The zone 1/2/3 group had longer hypothermic circulatory arrest times with greater use of antegrade cerebral perfusion (all P < .05). The perioperative and midterm outcomes were similar between the hemiarch and zone 1/2/3 arch groups, including 30-day mortality (7% vs 5%), rates of transient ischemic attack and stroke, incidence rates of reoperation for distal aortic pathology with a mean follow-up time of 3.5 years, and 5-year survival (79% [95% confidence interval, 69%-87%] vs 85% [95% confidence interval, 71%-93%]). However the hemiarch group had a trend of increased cumulative incidence of reoperation (8-year, 23% vs 9%; P = .33). CONCLUSIONS: In acute type A aortic dissection, dissection of arch branches alone should not be an indication for routine zone 1/2/3 arch replacement; however zone 1/2/3 arch replacement could be considered to prevent future reoperations in select patients.

Influence of Age on Longevity of a Stentless Aortic Valve.

BACKGROUND: The longevity of a stentless valve in a younger population (20-60 years old) is unknown. METHODS: From 1992 to 2015, 1947 patients underwent aortic valve/root replacement for aortic stenosis, insufficiency, root aneurysm, or aortic dissection with stentless bioprostheses (median size, 26 mm). At operation 105 patients were <40 years old, 528 were 40 to 59, 860 were 60 to 74, and 454 were ≥75 years. The data were obtained through chart review, administered surveys, and the National Death Index. RESULTS: The 30-day mortality rate was 2.6%. During follow-up 807 patients (41%) died before reoperation, 993 (51%) were alive without reoperations because of deterioration, and 113 patients (5.8%) underwent reoperation for structural valve deterioration. After adjusting death and reoperation for non-structural valve deterioration causes as competing risks, the cumulative incidence of reoperation was significantly different between the younger groups (<40, 40-59) and the older groups (60-74, ≥75; P < .0001) but not inside the younger (<40 vs 40-59) or older (60-74 vs ≥75) group. The significant hazard ratio of reoperation for <40 versus ≥75 years of age was 12, <40 versus 60 to 74 was 4, 40 to 59 versus 60 to 74 was 3, and 40 to 59 versus ≥75 was 9 (P ≤ .01). The 10- and 15-year survival in the entire cohort was 53% and 29%, respectively. CONCLUSIONS: The stentless aortic valve provides satisfactory durability as a conduit for aortic valve/root replacement for patients who prefer a bioprosthesis. However it should be judiciously considered for patients younger than 60 years because of an increased incidence of reoperation for structural valve deterioration.

Clinical Implications of Identifying Pathogenic Variants in Individuals With Thoracic Aortic Dissection.

BACKGROUND: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or family members. METHODS: We performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity. RESULTS: Twenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 versus 57 years), higher rates of root aneurysm (54% versus 30%), less hypertension (15% versus 57%), lower rates of smoking (19% versus 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed that pathogenic variant carrier status was significantly associated with age <50 (odds ratio [OR], 5.5; 95% CI, 1.6-19.7), no history of hypertension (OR, 5.6; 95% CI, 1.4-22.3), and family history of aortic disease (mother: OR, 5.7; 95% CI, 1.4-22.3, siblings: OR, 5.1; 95% CI, 1.1-23.9, children: OR, 6.0; 95% CI, 1.4-26.7). CONCLUSIONS: Clinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with a thoracic aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset <50 years, family history of thoracic aortic disease, and no history of hypertension.

Short- and long-term outcomes of aortic root repair and replacement in patients undergoing acute type A aortic dissection repair: Twenty-year experience.

OBJECTIVE: The study objective was to evaluate the perioperative and long-term outcomes of aortic root repair and aortic root replacement and provide evidence for root management in acute type A aortic dissection. METHODS: From 1996 to 2017, 491 patients underwent aortic root repair (n = 307) or aortic root replacement (n = 184) (62% bioprosthesis) for acute type A aortic dissection. Indications for aortic root replacement were intimal tear at the aortic root, root measuring 4.5 cm or more, connective tissue disease, or unrepairable aortic valvulopathy. Primary outcomes were in-hospital mortality, long-term survival, and reoperation rate for root pathology. RESULTS: Patients' median age was 61 years and 56 years in the aortic root repair group and aortic root replacement group, respectively. The aortic root replacement group had more renal failure requiring dialysis, previous cardiac intervention or surgery, heart failure, coronary malperfusion syndrome, acute myocardial infarction, and severe aortic insufficiency, as well as concomitant coronary artery bypass grafting, tricuspid valve repair, and longer cardiopulmonary bypass and aortic crossclamp times but similar arch procedures. Perioperative outcomes were similar in the aortic root repair and aortic root replacement groups, including in-hospital mortality (8.5% and 8.2%), new-onset renal failure requiring permanent dialysis, stroke, myocardial infarction, and sepsis. Kaplan-Meier 10-year survival was 62% and 65%, and the 15-year cumulative incidence of reoperation was 11% and 7% in the aortic root repair and aortic root replacement groups, respectively. The primary indication for root reoperation was aortic root aneurysm in the aortic root repair group and bioprosthetic valve deterioration in the aortic root replacement group. CONCLUSIONS: Aortic root repair and aortic root replacement are appropriate surgical options for acute type A aortic dissection repair with favorable short- and long-term outcomes. Aortic root replacement should be performed for patients with acute type A aortic dissection presenting with an intimal tear at the aortic root, root aneurysm 4.5 cm or greater, connective tissue disease, or unrepairable aortic valvulopathy.

Late outcomes of strategic arch resection in acute type A aortic dissection.

OBJECTIVE: To compare perioperative and long-term outcomes in patients undergoing hemiarch and aggressive arch replacement for acute type A aortic dissection (ATAAD). METHODS: From 1996 to 2017, we compared outcomes of hemiarch (n = 322) versus aggressive arch replacements (zones 2 and 3 arch replacement with implantation of 2-4 arch branches, n = 150) in ATAAD. Indications for aggressive arch were arch aneurysm >4 cm or intimal tear in the aortic arch that was not resectable by hemiarch replacement, or dissection of arch branches with malperfusion. RESULTS: Patients in the aggressive arch group were significantly younger (mean age: 57 vs 61 years old) and had significantly longer hypothermic circulatory arrest, cardiopulmonary bypass, and aortic crossclamp times. There were no significant differences in perioperative outcomes between hemiarch and aggressive arch groups, including 30-day mortality (5.3% vs 7.3%, P = .38) and postoperative stroke rate (7% vs 7%, P = .96). Over 15 years, Kaplan-Meier survival was similar between hemiarch and aggressive arch groups (log-rank P = .55, 10-year survival 70% vs 72%). Given death as a competing factor, incidence rates of reoperation over 15 years (2.1% vs 2.0% per year, P = 1) and 10-year cumulative incidence of reoperation (14% vs 12%, P = .89) for arch and distal aorta pathology were similar between the 2 groups. CONCLUSIONS: Both hemiarch and aggressive arch replacement are appropriate approaches for select patients with ATAAD. Aggressive arch replacement should be considered for an arch aneurysm >4 cm or an intimal tear at the arch unable to be resected by hemiarch replacement, or dissection of the arch branches with malperfusion.

A novel homozygous ABCA1 variant in an asymptomatic man with profound hypoalphalipoproteinemia.

Low high-density lipoprotein cholesterol (HDL-C) can be caused by several acquired secondary causes as well as primary genetic disorders. However, only a few conditions are associated with profoundly reduced levels below 10 mg/dL. We present an unusual case of a healthy man with severely decreased HDL-C because of a novel homozygous variant causing a Proline > Arginine amino acid change at position 1412 in the ATP-binding cassette transporter A1 gene. Homozygous variations in ATP-binding cassette transporter A1 typically cause Tangier disease, a rare autosomal recessive condition linked with several other abnormalities (eg, enlarged discolored tonsils). Despite having an HDL-C below 10 mg/dL, our patient presented without any other clinical symptoms or physical signs suggestive of Tangier disease. This case of presumptive Tangier disease adds support to the growing body of evidence that this genetic disorder may have greater phenotypic heterogeneity along with a more varied presentation than traditionally considered.

Aortic Valve Reoperation After Stentless Bioprosthesis: Short- and Long-Term Outcomes.

BACKGROUND: Limited data are available regarding outcomes for stentless aortic valve reoperation. The reported reoperative mortality has been unacceptably high. METHODS: Between 1997 and 2017, a retrospective analysis was performed on 143 patients who underwent open aortic valve reoperations for failed stentless aortic valve bioprostheses. We evaluated both short-term and long-term outcomes on this cohort of patients. RESULTS: Bicuspid aortic valve was present in 107 of 143 patients (75%) at the time of the initial Freestyle (Medtronic, Minneapolis, MN) procedure, and 120 of 143 patients (84%) underwent a modified inclusion aortic root replacement procedure. The interval from first operation to reoperation was 9 years (range, 5.4 to 11.8), which was significantly shorter for patients with infectious endocarditis (4.1 years; range, 1.8 to 7.1) compared with patients with structural valvular deterioration (10.4 years; range, 8.1 to 12.4, p < 0.001). The median age at the time of reoperation was 59 years (range, 50 to 67). Aortic valve reoperation was performed for structural valve deterioration in 68% cases compared with 32% for infectious prosthetic valve endocarditis. Concomitant surgery included coronary artery bypass (13%), mitral valve surgery (4%), and ascending aorta and arch replacement (42%). The 30-day and inhospital mortality was 1% and 2%, respectively. The composite outcome including myocardial infarction, stroke, new-onset renal failure on hemodialysis, and operative mortality was 4%. The 5-year and 10-year Kaplan-Meier survival after reoperation for failed stentless valve was 83% (95% confidence interval: 73% to 89%) and 57% (95% confidence interval: 36% to 74%). CONCLUSIONS: Aortic valve reoperation after stentless valve implantation can be performed with low operative mortality and favorable long-term survival.

Rapidly progressive atherosclerosis after domino liver transplantation from a teenage donor with homozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by impaired clearance of low-density lipoprotein cholesterol. Given limitations in pharmacologic therapy and the significant morbidity and mortality associated with this disease, liver transplantation may be offered to select homozygous FH patients in childhood in an effort to slow progression of atherosclerotic cardiovascular disease. In rare cases, domino liver transplantation can be performed, transplanting the livers of patients with various metabolic disorders into elderly recipients whose projected survival precludes prolonged waiting on the transplant list. Herein, we report a case of domino liver transplantation using the liver of a 14-year-old boy with homozygous FH into a 65-year-old man with primary sclerosing cholangitis and cirrhosis who developed rapidly progressive atherosclerotic cardiovascular disease involving the arteries of his proximal bilateral lower extremities, carotid arteries and superior mesenteric artery.

Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve.

Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.