IL-11 is a crucial determinant of cardiovascular fibrosis.

Fibrosis is a common pathology in cardiovascular disease. In the heart, fibrosis causes mechanical and electrical dysfunction and in the kidney, it predicts the onset of renal failure. Transforming growth factor ß1 (TGFß1) is the principal pro-fibrotic factor, but its inhibition is associated with side effects due to its pleiotropic roles. We hypothesized that downstream effectors of TGFß1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicity. Here we show, using integrated imaging-genomics analyses of primary human fibroblasts, that upregulation of interleukin-11 (IL-11) is the dominant transcriptional response to TGFß1 exposure and required for its pro-fibrotic effect. IL-11 and its receptor (IL11RA) are expressed specifically in fibroblasts, in which they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il-11 injection causes heart and kidney fibrosis and organ failure, whereas genetic deletion of Il11ra1 protects against disease. Therefore, inhibition of IL-11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These results reveal a central role of IL-11 in fibrosis and we propose that inhibition of IL-11 is a potential therapeutic strategy to treat fibrotic diseases.

Homemade Candy Plug Using a Zenith Alpha Thoracic Stent-Graft for False Lumen Distal Occlusion in Acute-on-Chronic Type B Aortic Dissection.

Purpose: To report a candy-plug technique using a Zenith Alpha stent-graft to occlude the distal false lumen in a patient with a complicated chronic type B aortic dissection. Case Report: A 50-year-old male smoker presented with chest pain due to rapidly growing complicated chronic type B aortic dissection. Computed tomography angiography (CTA) showed the dissection extending from distal to the origin of the left subclavian artery (LSA) down to the left femoral artery. There was fusiform aneurysmal dilatation of the proximal descending aorta measuring up to 5.8 cm in diameter. He underwent left carotid-subclavian artery bypass, thoracic endovascular aortic repair with a Zenith Alpha stent-graft, a left common carotid artery chimney, and embolization of the proximal LSA. Serial CTA showed persistent false lumen flow. A decision was made to occlude the distal large false lumen using the candy-plug technique. A 44×125-mm Zenith Alpha stent-graft was used to prepare the candy plug. A gutter leak and a type Ia endoleak were embolized via a left brachial artery approach. At 2.5 years, imaging showed the candy plug in position, no endoleak, and the thrombosed false lumen in the thoracic aorta reduced in size. Conclusion: The candy-plug technique is useful in facilitating complete occlusion of the false lumen in chronic aortic dissection, which avoids an open procedure and the risk of higher morbidity.

Therapeutic Hypothermia May Improve Neurological Outcomes in Extracorporeal Life Support for Adult Cardiac Arrest.

BACKGROUND: Limited data exists on patients receiving therapeutic hypothermia during extracorporeal life support (ECLS). We investigated outcomes and prognostic factors in these patients. METHODS: A retrospective review was conducted for 225 consecutive adult patients treated with ECLS between July 2003 and January 2016. Extracorporeal life support was initiated for refractory cardiac arrest (>10 mins) in 79 patients (35.1%). Patient demographics, ECLS-related complications, in-hospital mortality and neurological outcomes were analysed. RESULTS: The mean age was 49.9±12.4 years. Sixty-two patients (78.5%) were male. The mean duration of CPR and ECLS were respectively, 32.0±23.3 mins and 5.4±4.0 days. Therapeutic hypothermia (34oC) was maintained for 24hours in 14 patients (17.7%). Thirty-five patients (44.3%) were weaned off ECLS. Twenty-one patients (26.6%) survived to hospital discharge with 16 (20.3%) recovering good neurological function. Compared to ECLS at normothermia, neurologically favourable survival was higher in the hypothermia group (42.9% vs 15.4%, p=0.020). Multivariable analysis identified a non-shockable rhythm [odds ratio (OR) 5.1, confidence interval (CI) 1.5-16.8], ischaemic hepatitis (OR 6.2, CI 1.1-33.6) and hypoxic ischaemic encephalopathy (OR 5.1, CI 1.5-17.1) as predictors of in-hospital mortality. Therapeutic hypothermia (OR 4.9, CI 1.2-20.4) and acute renal failure (OR 0.19, CI 0.05-0.70) were predictors of neurologically favourable survival. CONCLUSIONS: In this report of patients treated with ECLS, in-hospital survival and survival with good neurological performance were 26.6% and 20.3% respectively. A non-shockable rhythm, ischaemic hepatitis and hypoxic ischaemic encephalopathy were predictors of in-hospital mortality. Therapeutic hypothermia during ECLS was associated with improved neurological outcomes.

Network Meta-Analysis Comparing Transcatheter, Minimally Invasive, and Conventional Surgical Aortic Valve Replacement.

The landscape of aortic valve replacement (AVR) has evolved dramatically over the years, but time-varying outcomes have yet to be comprehensively explored. This study aimed to compare the all-cause mortality among 3 AVR techniques: transcatheter (TAVI), minimally invasive (MIAVR), and conventional AVR (CAVR). An electronic literature search was performed for randomized controlled trials (RCTs) comparing TAVI with CAVR and RCTs or propensity score-matched (PSM) studies comparing MIAVR with CAVR or MIAVR to TAVI. Individual patient data for all-cause mortality were derived from graphical reconstruction of Kaplan-Meier curves. Pairwise comparisons and network meta-analysis were conducted. Sensitivity analyses were performed in the TAVI arm for high risk and low/intermediate risk, as well as patients who underwent transfemoral (TF) TAVI. A total of 27 studies with 16,554 patients were included. In the pairwise comparisons, TAVI showed superior mortality to CAVR until 37.5 months, beyond which there was no significant difference. When restricted to TF TAVI versus CAVR, a consistent mortality benefit favoring TF TAVI was seen (shared frailty hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.76 to 0.98, p = 0.024). In the network meta-analysis involving majority PSM data, MIAVR demonstrated significantly lower mortality than TAVI (HR = 0.70, 95% CI = 0.59 to 0.82) and CAVR (HR = 0.69, 95% CI = 0.59 to 0.80); this association remained compared with TF TAVI but with a lower extent of benefit (HR = 0.80, 95% CI = 0.65 to 0.99). In conclusion, the initial short- to medium-term mortality benefit for TAVI over CAVR was attenuated over the longer term. In the subset of patients who underwent TF TAVI, a consistent benefit was found. Among majority PSM data, MIAVR showed improved mortality compared with TAVI and CAVR but less than the TF TAVI subset, which requires validation by robust RCTs.

Long-term prognosis in patients with end-stage renal disease after coronary artery bypass grafting.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Coronary artery bypass grafting (CABG) is beneficial in selected patients with ESRD. This study investigates the survival outcomes and prognostic factors in ESRD patients who underwent CABG. METHODS: A retrospective analysis was performed for 149 patients with ESRD who underwent isolated CABG between 2006 and 2015. RESULTS: Mean age was 59.4±8.7 years and 106 patients (71.1%) were male. Operative mortality occurred in 20 patients (13.4%). Overall survival was 81.1%±3.2% at 1 year, 41.5%±4.3% at 5 years and 19.2%±4.2% at 10 years. Median survival was 4.3 years. Multivariable analysis identified age [P=0.001, odds ratio (OR): 1.15 per 1-year increase, 95% confidence interval (CI): 1.06-1.25], preoperative left ventricular ejection fraction (LVEF) (P=0.020, OR: 0.94, 95% CI: 0.89-0.99) and non-elective status of operation (P=0.049, OR: 3.34, 95% CI: 1.00-11.1) as predictors of operative mortality. Cox regression analysis identified age [P<0.001, hazard ratio (HR): 1.05 per 1-year increase, 95% CI: 1.03-1.08], New York Heart Association (NYHA) class III or IV status (P=0.010, HR: 1.75, 95% CI: 1.15-2.67) and the use of a left internal mammary artery (LIMA) to left anterior descending artery (LIMA-LAD) graft (P=0.029, HR: 0.42, 95% CI: 0.19-0.92) as factors influencing long-term survival. CONCLUSIONS: CABG is associated with high operative mortality and poor long-term survival in ESRD patients. Age and NYHA class influenced late survival. LIMA-LAD grafting conferred a long-term survival advantage.

Restrictive mitral valve annuloplasty for chronic ischaemic mitral regurgitation: outcomes of flexible versus semi-rigid rings.

BACKGROUND: Restrictive mitral annuloplasty is the mainstay of surgical correction of chronic ischaemic mitral regurgitation (CIMR). Long-term data on the various types of annuloplasty rings is limited. The aim of this study was to investigate the clinical and echocardiographic outcomes of restrictive mitral annuloplasty in patients with CIMR, comparing the use of flexible versus semi-rigid annuloplasty rings. METHODS: A retrospective review was conducted for 133 patients with CIMR who underwent restrictive mitral annuloplasty at our institution between 1999 and 2015. Patient demographics and postoperative outcomes were analyzed. RESULTS: Mean age was 61.9±9.2 years and 103 patients (77.4%) were male. All patients underwent coronary artery bypass grafting, with a mean of 3.3±0.8 grafts. Flexible rings was implanted in 39 patients (29.3%, group F) and semi-rigid rings in 94 (70.7%, group R). Preoperative New York Heart Association class was III/IV in 104 patients (78.2%). Mean preoperative left ventricular ejection fraction was 28.8%±10.2%. Preoperative mitral regurgitation was moderate in 51 patients (38.3%) and severe in 82 (61.7%). In-hospital mortality occurred in 11 patients (8.3%). Overall survival at 1, 5 and 10 years were, respectively, 86.4%, 69.7% and 45.9%. At 10 years, overall survival (group F 53.1%, group R 40.0%, P=0.330) and freedom from moderate to severe MR (group F 53.1%, group R 53.8%, P=0.725) did not differ significantly. Freedom from hospitalization for heart failure was 59.3%. Left ventricular reverse remodelling, defined as a reduction of left ventricular end-systolic volume index >15%, occurred more commonly in Group R (51.1%) compared to Group F (23.1%), P=0.003. CONCLUSIONS: Restrictive mitral annuloplasty was associated with an operative mortality of 8.3%. Heart failure symptoms and significant MR recur in approximately 40% of patients after 10 years. Survival remained suboptimal and was not influenced by the type of annuloplasty ring.

Endovascular Retrieval of Entrapped Elephant Trunk Graft During Complex Hybrid Aortic Arch Repair.

Entrapment of the elephant trunk graft within the false lumen is a rare complication of surgical repair of an aortic dissection. This is normally retrieved by emergent open surgery. We describe a technique of endovascular retrieval of the dislodged graft, during hybrid aortic arch repair. The elephant trunk was cannulated through and through from a femoral access and the free end of the wire was snared and retrieved from a brachial access. The wire was externalised from both accesses and was used to reposition the graft into the true lumen using a body flossing technique.

Does preoperative statin therapy prevent postoperative atrial fibrillation in patients undergoing cardiac surgery?

A best evidence topic was written according to a structured protocol. The question addressed was: does preoperative statin therapy prevent postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery? There were 445 papers found using the reported search. From these, 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This paper includes three systematic reviews with meta-analysis, five randomized controlled trials and four retrospective studies. All the papers compared either all or some of the following postoperative complications: mortality, morbidity, AF, length of hospital stay (intensive care unit and hospital) and inflammatory markers. The largest study in this paper includes a systematic review of 91 491 patients that showed a reduction in postoperative AF with preoperative statin therapy (OR = 0.71, 95% CI 0.61-0.82, P <0.0001). However, the durations (3 days to 2 months preoperatively), doses and types of preoperative statin differed between these papers. Although the majority of studies (10 of 12) support the use of statins preoperatively, 2 studies found no association between preoperative statin therapy and the reduction of postoperative AF. In conclusion, the available evidence suggests that preoperative statin therapy in patients undergoing elective cardiac surgery is associated with the following: (1) a lower incidence and risk of developing postoperative AF, (2) reduced stroke, (3) a shorter hospital stay and (4) reduced levels of inflammatory markers postoperatively. However, while the evidence supports the use of statins preoperatively, the optimal duration, dose and type of statin cannot be concluded from this review.

Surgical management of infective endocarditis: an analysis of early and late outcomes.

OBJECTIVES: To review our experience of surgical management of infective endocarditis (IE) over a 13-year period and analyse the outcomes and associated prognostic factors. METHODS: A retrospective review was conducted for 191 consecutive patients who underwent surgery for native and prosthetic valve endocarditis (PVE) between January 2000 and December 2012. Surgical outcomes were reviewed to include survival and postoperative complications. Follow-up was complete for 172 of 179 patients (96.1%) surviving to hospital discharge, with a mean follow-up of 6.6 ± 3.7 years. RESULTS: Mean age was 47.4 ± 14.9 years with 113 (63.9%) males. Native valve endocarditis was present in 177 patients (92.7%). Sixty-three patients (33.0%) presented with embolic complications. The brain was the most common site of embolism, involving 25 patients (13.1%). Streptococcus viridans was the most common infective organism, isolated in 68 patients (35.7%), followed by Staphylococcus aureus in 30 patients (15.7%). Eighty-seven patients (45.5%) had active endocarditis at the time of surgery. The mitral valve was infected in 136 patients (71.2%), the aortic valve in 66 (34.6%), the tricuspid valve in 29 (15.2%) and multiple valves in 38 (19.9%). Nineteen patients (9.9%) were intravenous drug users (IVDU). Twelve IVDUs (63.2%) suffered from tricuspid valve IE, compared with 7 of 162 patients (4.3%) in the non-IVDU population (P < 0.001). The most common indication for early surgery was intractable cardiac failure. Twelve patients (6.3%) died during the hospital stay for surgical treatment of IE. Logistic multivariate analysis identified preoperative creatinine clearance and stroke as independent predictors of in-hospital mortality. Overall 10-year survival and freedom from valve-related reoperation were 74.8 and 90.3%, respectively. Age, PVE, S. aureus endocarditis and postoperative left ventricular ejection fraction (LVEF) ≤45% were factors influencing long-term survival. CONCLUSIONS: Surgical management of endocarditis continues to be challenging and is associated with significant morbidity and mortality. This report of 191 patients who underwent valve surgery for IE shows that in-hospital mortality is influenced by preoperative renal function and stroke at the time of presentation. The optimal timing for surgery in patients with stroke remains controversial. Long-term survival was negatively influenced by increasing age, moderate to severely impaired LVEF, prosthetic valve IE and S. aureus infection.

Outcome and survival analysis of surgical repair of post-infarction ventricular septal rupture.

BACKGROUND: To review the experience of surgical repair of post-infarction ventricular septal rupture (VSR) and analyze the associated outcomes and prognostic factors. METHODS: Following approval from the Singhealth Centralised Institutional Review Board (reference: 2011/881/C), a retrospective review was performed on 38 consecutive patients who had undergone surgical repair of post-infarction VSR between 1999 and 2011. Continuous variables were expressed as either mean ± standard deviation or median with 25th and 75th percentiles. These were compared using two-tailed t-test or Mann-Whitney U test respectively. Categorical variables were compared using chi-square or Fisher's exact test. To identify predictors of operative mortality, univariate analysis of perioperative variables followed by multivariate analysis of significant univariate risk factors was performed. A two-tailed p-value < 0.05 was used to indicate statistical significance. RESULTS: Mean age was 65.7 ± 9.4 years with 52.6% males. The VSR was anterior in 28 (73.7%) and posterior in 10 patients. Median interval from myocardial infarction to VSR was 1 day (1, 4). Pre-operative intra-aortic balloon pump was inserted in 37 patients (97.8%). Thirty-six patients (94.7%) underwent coronary angiography.Thirty-five patients (92.1%) underwent patch repair. Mean aortic cross clamp time was 82 ± 40 minutes and mean cardiopulmonary bypass time was 152 ± 52 minutes. Coronary artery bypass grafting (CABG) was performed in 19 patients (50%), with a mean of 1.5 ± 0.7 distal anastomoses. Operative mortality within 30 days was 39.5%.Univariate analysis identified emergency surgery, New York Heart Association (NYHA) class, inotropic support, right ventricular dysfunction, EuroSCORE II, intra-operative red cell transfusion, post-operative renal failure and renal replacement therapy (RRT) as predictors of operative mortality. Multivariate analysis identified NYHA class and post-operative RRT as predictors of operative mortality.Ten year overall survival was 44.4 ± 8.4%. Right ventricular dysfunction, LVEF and NYHA class at presentation were independent factors affecting long-term survival. Concomitant CABG did not influence early or late survival. CONCLUSIONS: Surgical repair of post-infarction VSR carries a high operative mortality. NYHA class at presentation and post-operative RRT are predictors of early mortality. Right ventricular dysfunction, LVEF and NYHA class at presentation affect long-term survival. Concomitant CABG does not improve survival.

Iliofemoral anatomy among Asians: implications for transcatheter aortic valve implantation.

BACKGROUND/OBJECTIVES: This study aims to examine iliofemoral anatomy and predictors of vessel size and tortuosity in Asian patients as transfemoral transcatheter aortic valve implantation (TAVI) may be limited by the smaller Asian physique. METHODS: Characteristics and vessel dimensions of 549 patients undergoing ultrasonography were reviewed. The minimal luminal diameter (MLD) along the iliofemoral vasculature of each side was identified and the larger of the two sides was used to determine suitability for transfemoral TAVI. RESULTS: The mean age was 66 ± 11 years (68% males). Mean iliac MLD was 7.6 ± 1.7 mm, females smaller than males (7.2 ± 1.7 vs 7.8 ± 1.7, p<0.001). Mean iliac MLD decreased with age: 7.9 ± 1.7 mm, 7.4 ± 1.9 mm and 7.3 ± 1.6mm for ages <70 years, 70-79 years and ≥ 80 years respectively (p=0.038). Mean femoral MLD was 7.0 ± 1.7 mm, females smaller than males (6.3 ± 1.5mm vs 7.3 ± 1.8mm, p<0.001). Females were more likely than males to have iliac and femoral MLD <6mm (20% vs 12%, p=0.019 and 34% vs 21%, p=0.001). Independent predictors of smaller iliofemoral dimensions were female gender, lower body surface area, diabetes mellitus, dyslipidemia and smoking history. Significant iliac tortuosity was present in 11.8%, more frequent in males than females (15% vs 6%, p=0.005), and in those with logistic EuroSCORE ≥ 15 than <15 (27% vs 10%, p=0.001). CONCLUSIONS: This study establishes the mean iliac and femoral artery diameters in a cohort of relatively young Asian patients. Age and female gender were associated with smaller vessel dimension and several independent predictors of smaller vasculature and tortuosity were identified. These results have implications for TF TAVI in Asia.

Tracheobronchial obstruction as a result of mediastinal mass.

A 21-year-old woman presented with almost complete extrinsic airway obstruction due to a massive mediastinal tumor. Venovenous extracorporeal membrane oxygenation support for 3 days with concurrent chemotherapy allowed time for tumor shrinkage, ventilation via the endotracheal route, and subsequent successful extubation on the fifth day.