Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been ...described in small reports.
An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type.
TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.
Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although ...percutaneous closure is increasingly undertaken.
Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older 72 (64-77) vs. 67 (61-73) years, P < 0.001 and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach aHR 1.44 (1.01-2.05), P = 0.042, and number of vessels with coronary artery disease aHR 1.22 (1.01-1.47), P = 0.043 were independently associated with long-term mortality.
Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.
Transcatheter aortic and pulmonary valves have been used to treat stenosis or regurgitation after prior surgical tricuspid valve (TV) replacement or repair. Little is known about intermediate-term ...valve-related outcomes after transcatheter tricuspid valve replacement (TTVR), including valve function, thrombus, and endocarditis.
The authors sought to evaluate mid-term outcomes in a large cohort of patients who underwent TTVR after surgical TV repair or replacement, with a focus on valve-related outcomes.
Patients who underwent TTVR after prior surgical TV replacement or repair were collected through an international registry. Time-related outcomes were modeled and risk factors assessed.
Data were collected for 306 patients who underwent TTVR from 2008 through 2017 at 80 centers; 52 patients (17%) had a prior history of endocarditis. Patients were followed for a median of 15.9 months after implantation (0.1 to 90 months), with 64% of patients estimated to be alive without TV reintervention or a valve-related event at 3 years. The cumulative 3-year incidence of death, reintervention, and valve-related adverse outcomes (endocarditis, thrombosis, or significant dysfunction) were 17%, 12%, and 8%, respectively. Endocarditis was diagnosed in 8 patients 2 to 29 months after TTVR, for an annualized incidence rate of 1.5% per patient-year (95% confidence interval: 0.45% to 2.5%). An additional 8 patients were diagnosed with clinically relevant valve thrombosis, 3 in the short term, 2 within 2 months, and 3 beyond 6 months. Only 2 of these 8 patients received anticoagulant therapy before thrombus detection (p = 0.13 vs. patients without thrombus). Prior endocarditis was not a risk factor for reintervention, endocarditis, or valve thrombosis, and there was no difference in valve-related outcomes according to TTVR valve type.
TV dysfunction, endocarditis, and leaflet thrombosis were uncommon after TTVR. Patients with prior endocarditis were not at higher risk for endocarditis or other adverse outcomes after TTVR, and endocarditis occurred with similar frequency in different valve types. Though rare, leaflet thrombosis is an important adverse outcome, and further study is necessary to determine the appropriate level of prophylactic therapy after TTVR.
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We sought to describe the acute results and short- to medium-term durability of transcatheter tricuspid valve-in-valve (TVIV) implantation within surgical bioprostheses among patients with Ebstein ...anomaly (EA). Cases were identified from a voluntary, multicenter, international registry of 29 institutions that perform TVIV. Demographic, clinical, procedural, and follow-up data were analyzed. Eighty-one patients with EA underwent TVIV from 2008 to 2016. Thirty-four patients (42%) were New York Heart Association (NYHA) class 3/4 at time of TVIV. The most common indication for TVIV was the presence of moderate or severe tricuspid regurgitation (40%). Most patients received a Melody valve (64%). TVIV was ultimately successful in all patients, and there was no procedural mortality. Four patients (5%) developed acute valve thrombosis, 4 patients (5%) developed endocarditis, and 9 patients (11%) developed valve dysfunction not related to thrombosis or endocarditis. Eight patients (10%) underwent reintervention (2 transcatheter, 6 surgical) due to thrombosis (3), endocarditis (2), other valve dysfunction (2), and patient-prosthesis mismatch without valve dysfunction (1). Among 69 patients who were alive without reintervention at latest follow-up, 96% of those with NYHA status reported were class 1/2, a significant improvement from baseline (62% NYHA class 1/2, p <0.001). In conclusion, transcatheter TVIV offers a low-risk, minimally invasive alternative to surgical tricuspid valve re-replacement in patients with EA and a failing tricuspid valve bioprosthesis.
Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the ...effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.
We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.
Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.
Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.
British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.
To bring together patients, parents, charities and clinicians in a Priority Setting Partnership to establish national clinical priorities for research in children and adults with congenital heart ...disease.
The established James Lind Alliance methodology was used to identify and prioritise research on the management of congenital heart disease, focusing on diagnosis, treatment and outcomes. An initial open survey was used to gather potential uncertainties which were filtered, categorised, converted into summary questions and checked against current evidence. In a second survey, respondents identified the unanswered questions most important to them. At two final workshops, patients, parents, charities and healthcare professionals agreed the top 10 lists of priorities for child/antenatal and adult congenital heart disease research.
524 respondents submitted 1373 individual questions, from which 313 out of scope or duplicate questions were removed. The remaining 1060 questions were distilled into summary questions and checked against existing literature, with only three questions deemed entirely answered and removed. 250 respondents completed the child/antenatal survey (56 uncertainties) and 252 completed the adult survey (47 uncertainties). The questions ranked the highest by clinicians and non-clinicians were taken forward to consensus workshops, where two sets of top 10 research priorities were agreed.
Through an established and equitable process, we determined national clinical priorities for congenital heart disease research. These will be taken forward by specific working groups, a national patient and public involvement group, and through the establishment of a UK and Ireland network for collaborative, multicentre clinical trials in congenital heart disease.
Summary
Background
Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti‐TNF therapy for IBD, with ...consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation.
Aim
To establish outcomes following anti‐TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta‐analysis.
Methods
A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis UC) and IBD unclassified (IBDU) withdrawn from anti‐TNF for sustained remission. Meta‐analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC).
Results
Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis hazard ratio (HR) 2.78 for age <22 years, white cell count (HR 3.22 for >5.25 × 109/L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta‐analysis, estimated 1‐year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti‐TNF was successful in 88% for CD and 76% UC/IBDU.
Conclusions
Assimilation of all available data reveals remarkable homogeneity. Approximately one‐third of patients with IBD flare within 12 months of withdrawal of anti‐TNF therapy for sustained remission.
The aim of this study was to describe the clinical impact of management of coarctation of the aorta by transcatheter stent placement in the context of longer term management of systemic hypertension. ...In the long term, poor outlook associated with untreated coarctation of the aorta is likely to relate to uncontrolled systemic hypertension. Transcatheter stent placement to treat native and recurrent coarctation of the aorta is an established therapy in adolescents and adults. There remains confusion about longer term outcomes, particularly the relation between procedural success and improvement in blood pressure (BP) control. Improvement in lifelong systemic BP control after transcatheter stent placement remains unproved. Forty patients underwent transcatheter stent placement over a 10-year period (2001 to 2010) at the Yorkshire Heart Centre. The average age at the time of procedure was 25 years (range 14 to 57). There was a reduction in peak systolic gradient across the coarcted segment from 25 to <10 mm Hg in 35 of 39 patients. After stent placement, there was a significant improvement in systolic BP control at early and later follow-up (mean 155 mm Hg before the procedure and 134 mm Hg at 2.81-year follow-up, p <0.0001). There was 1 early procedural adverse event (stent embolization) and 1 late adverse event (lower limb claudication). In conclusion, transcatheter stent placement for the management of aortic coarctation is associated with a reduction in systolic BP that is maintained over the medium term. A significant minority of patients remain significantly hypertensive, and the best management strategy for this group of patients remains unclear.
Primary pulmonary hypertension (PPH), characterized by obstruction of pre-capillary
pulmonary arteries, leads to sustained elevation of pulmonary arterial pressure
(mean >25 mm Hg at rest or >30 mm ...Hg during exercise). The
aetiology is unknown, but the histological features reveal proliferation of
endothelial and smooth muscle cells with vascular remodelling
(Fig. 1). More than one affected relative has been identified
in at least 6% of cases (familial PPH, MIM 178600). Familial
PPH (FPPH) segregates as an autosomal dominant disorder with reduced penetrance
and has been mapped to a locus designated PPH1 on 2q33, with no evidence
of heterogeneity. We now show that FPPH is caused by
mutations in BMPR2, encoding a TGF-β type II receptor (BMPR-II).
Members of the TGF-β superfamily transduce signals by binding to heteromeric
complexes of type I and II receptors, which activates serine/threonine kinases,
leading to transcriptional regulation by phosphorylated Smads.
By comparison with in vitro studies, identified defects of BMPR-II
in FPPH are predicted to disrupt ligand binding, kinase activity and heteromeric
dimer formation. Our data demonstrate the molecular
basis of FPPH and underscore the importance in vivo of the TGF-β
signalling pathway in the maintenance of blood vessel integrity.†These authors contributed equally to this work.
*Micheala Aldred2, Christopher A. Brannon3, P. Michael Conneally4, Tatiana Foroud4, Neale Fretwell2, Radhika Gaddipati1, Daniel Koller4, Emily J. Loyd1, Neil Morgan2, John H. Newman1, Melissa A. Prince1, Carles Vilariño Güell2 & Lisa Wheeler1
1Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Division of Medical Genetics, Departments of Genetics and Medicine, University of Leicester, UK.
3Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
4Indiana University School of Medicine, Indianapolis, Indiana, USA.
Correspondence should be addressed to J.E.L. (e-mail: Jim.Loyd@mcmail.vanderbilt.edu), W.C.N. (e-mail: bill.nichols@chmcc.org) or R.C.T. (e-mail: rtrembat@hgmp.mrc.ac.uk).
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