Yeow Leng Chua

Electrophysiology of human cardiac atrial and ventricular telocytes

Telocytes (TCs) with exceptionally long cellular processes of telopodes have been described in human epicardium to act as structural supporting cells in the heart. We examined myocardial chamber‐specific TCs identified in atrial and ventricular fibroblast culture using immunocytochemistry and studied their electrophysiological property by whole‐cell patch clamp. Atrial and ventricular TCs with extended telopodes and alternating podoms and podomers that expressed CD34, c‐Kit and PDGFR‐β were identified. These cells expressed large conductance Ca2+‐activated K+ current (BKCa) and inwardly rectifying K+ current (IKir), but not transient outward K+ current (Ito) and ATP‐sensitive potassium current (KATP). The active channels were functionally competent with demonstrated modulatory response to H2S and transforming growth factor (TGF)‐β1 whereby H2S significantly inhibited the stimulatory effect of TGF‐β1 on current density of both BKCa and IKir. Furthermore, H2S attenuated TGF‐β1‐stimulated KCa1.1/Kv1.1 (encode BKCa) and Kir2.1 (encode IKir) expression in TCs. Our results show that functionally competent K+ channels are present in human atrial and ventricular TCs and their modulation may have significant implications in myocardial physiopathology.

Factors influencing radial artery size.

Size matching of radial artery conduits to coronary arteries is important as it affects the long-term patency. However, factors affecting radial artery size have not been adequately investigated. We retrospectively reviewed 327 consecutive patients who had duplex ultrasonography of their radial arteries over a 2-year period. There were 225 men and 102 women. The mean radial artery size was 2.45 ± 0.54 mm. The factors found to positively affect the size of the radial artery were sex, hypertension, and hyperlipidemia. Diabetes mellitus and age were found to negatively affect radial artery size. Renal disease, race, and smoking did not significantly influence the size of the radial artery. However, as the R squared of this model was insignificant, further studies need to be undertaken to determine other factors that may influence radial artery size.

A survivor of late prosthesis migration and rotation following percutaneous transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) has emerged as a viable alternative endovascular technique in selected patients with severe aortic stenosis, who are either inoperable or at high risk for surgical aortic valve replacement. We report a case of delayed displacement and rotation of an aortic bioprosthesis, 43 days after successful TAVI via the transfemoral approach, with the patient surviving the subsequent open heart surgery required for device retrieval.

Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts

Cardiac fibroblasts are crucial in pathophysiology of the myocardium whereby their aberrant proliferation has significant impact on cardiac function. Hydrogen sulphide (H2S) is a gaseous modulator of potassium channels on cardiomyocytes and has been reported to attenuate cardiac fibrosis. Yet, the mechanism of H2S in modulating proliferation of cardiac fibroblasts remains poorly understood. We hypothesized that H2S inhibits proliferative response of atrial fibroblasts through modulation of potassium channels. Biophysical property of potassium channels in human atrial fibroblasts was examined by whole‐cell patch clamp technique and their cellular proliferation in response to H2S was assessed by BrdU assay. Large conductance Ca2+‐activated K+ current (BKCa), transient outward K+ current (Ito) and inwardly rectifying K+ current (IKir) were found in human atrial fibroblasts. Current density of BKCa (IC50 = 69.4 μM; n = 6), Ito (IC50 = 55.1 μM; n = 6) and IKir (IC50 = 78.9 μM; n = 6) was significantly decreased (P < 0.05) by acute exposure to NaHS (a H2S donor) in atrial fibroblasts. Furthermore, NaHS (100–500 μM) inhibited fibroblast proliferation induced by transforming growth factor‐β1 (TGF‐β1; 1 ng/ml), Ang II (100 nM) or 20% FBS. Pre‐conditioning of fibroblasts with NaHS decreased basal expression of Kv4.3 (encode Ito), but not KCa1.1 (encode BKCa) and Kir2.1 (encode IKir). Furthermore, H2S significantly attenuated TGF‐β1–stimulated Kv4.3 and α‐smooth muscle actin expression, which coincided with its inhibition of TGF‐β–induced myofibroblast transformation. Our results show that H2S attenuates atrial fibroblast proliferation via suppression of K+ channel activity and moderates their differentiation towards myofibroblasts.

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

BackgroundTo review the experience of surgical repair of post-infarction ventricular septal rupture (VSR) and analyze the associated outcomes and prognostic factors.MethodsFollowing 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.ResultsMean 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.ConclusionsSurgical 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.

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.

Infected Coronary Artery Pseudoaneurysm After Repeated Percutaneous Coronary Intervention

Coronary stent infection is exceedingly rare, with only 23 reported cases. We present a patient with an everolimus-coated stent infection that led to an infected pseudoaneurysm in the left anterior descending artery. Medical therapy failed and the patient underwent emergent surgical intervention; however, he died of multiorgan failure after the operation.

Outcome and survival analysis of intestinal ischaemia following cardiac surgery

OBJECTIVES Intestinal ischaemia is an uncommon (<1%) but serious complication of cardiac surgery with a mortality rate exceeding 50%. Diagnosis of this potentially lethal condition can be difficult and requires a high index of suspicion. The purpose of this study was to analyse the outcomes and prognostic factors in patients who develop intestinal ischaemia following cardiac surgery. METHODS In a retrospective review from August 1999 to December 2010, we identified 31 out of 9925 (0.31%) consecutive patients who developed acute intestinal ischaemia following cardiac surgery at our tertiary centre. RESULTS The overall mortality was 71.0%. The operative mortality was 65.4% in patients who underwent a laparotomy. Survivors of this complication had surgical intervention earlier (7.4 ± 4.9 h) compared with the non-survivors (13.9 ± 11.1 h). A total of 35 perioperative variables were analysed. A univariate analysis identified 12 variables associated with an increased risk of mortality. Logistic multivariate analysis identified the preoperative logistic EuroSCORE and the base excess at the point of diagnosis of intestinal ischaemia as significant predictors of mortality. These factors may aid prognostication in this group of patients. CONCLUSIONS Despite the high mortality rates associated with intestinal ischaemia following cardiac surgery, early diagnosis and surgical intervention remain the only effective means to reduce mortality.

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.

Acquired right-to-left shunt through an atrial septal perforation with cyanosis after percutaneous transvenous mitral commissurotomy

Clinical Summary A 49-year-old woman with a history of longstanding rheumatic heart disease presented with breathlessness and cyanosis, as well as bilateral lower limb swelling, for 2 weeks. She had undergone closed mitral valvotomy 26 years ago and subsequent PTMC twice 14 and 4 years ago, respectively. Other significant medical histories are atrial fibrillation and diabetes mellitus. Recent transthoracic echocardiography (TTE) 1 year ago showed moderate mitral stenosis (MS) with a mitral valve area of 1.3 cm, mild mitral regurgitation (MR), severe tricuspid regurgitation (TR) with a pulmonary artery systolic pressure of 38 mm Hg, and a small atrial septal defect with left-to-right shunt, which was already shown on TTE 4 years ago after the second PTMC. Ejection fraction was 55%. She had mild congestive cardiac failure (CCF) with multiple hospital admissions within the last few months. She presented this admission with exacerbation of breathlessness and was found to be in CCF. She was centrally cyanosed, and oxygen saturation on room air was 80% to 86%. TTE revealed right-toleft shunt through an ASP of 0.7 cm in diameter, severe MS, trivial MR, and severe TR with a dilated annulus (Figure 1). Right heart study showed a mean right atrial pressure of 27 mm Hg and a pulmonary capillary wedge pressure of 22 mm Hg. Pulmonary artery systolic pressure was 51 mm Hg. The oximetric sampling showed 72% oxygen saturation in the left ventricle. The patient improved with diuresis and subsequently agreed to surgical intervention. Atrial septal repair with mitral valve replacement and tricuspid valve repair was performed with median sternotomy. On sternotomy, the right atrium was found to be enlarged and tense. Central