Greg Cranney

Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospital-based population

Modest elevations of circulating homocysteine are common in patients with vascular disease. We explored interrelations between total plasma homocysteine levels and mutations in genes for three key enzymes in methionine-homocysteine metabolism. Methyltetrahydrofolate reductase (MTHFR) 677C-->T, cystathionine beta synthase (CBS) 68-bp insertion at exon 8, and methionine synthase (MS) 2756A-->G were typed in 685 Australian caucasian patients aged < or =65 years with and without angiographically documented coronary artery disease (CAD). We also assessed associations between homocysteine levels and extracellular superoxide dismutase (EC-SOD) and other CAD risk factors. There were significant correlations between plasma total homocysteine, and EC-SOD (r = 0.170, p = 0.001 for men; r = 0.241, p = 0.003 for women) and LDL (r = 0.153, p = 0.001 for men; r = 0.132, p = 0.081 for women). Levels were also significantly higher among patients with unstable angina (15.30+/-0.44 micromol/l for men, 14.44+/-0.74 micromol/l for women) than those without angina (13.98+/-0.38 micromol/l for men, 13.41+/-0.98 micromol/l for women) or with stable angina (14.00+/-0.37 micromol/l for men, 12.88+/-0.71 micromol/l for women). There were no significant associations between the levels and the presence or severity of CAD. The mutant MTHFR homozygotes tended to have higher levels and those with the MS and CBS mutations tended to have lower levels. We conclude that there is a significant correlation between plasma homocysteine levels and EC-SOD suggesting that elevated homocysteine may exert oxidative stress and that levels are associated with unstable angina, but not the occurrence or extent of coronary stenosis. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabolism are modest.

Real-Time 3D Transesophageal Echocardiography for the Evaluation of Rheumatic Mitral Stenosis

OBJECTIVES The aims of this study were: 1) to assess the feasibility and reliability of performing mitral valve area (MVA) measurements in patients with rheumatic mitral valve stenosis (RhMS) using real-time 3-dimensional transesophageal echocardiography (3DTEE) planimetry (MVA(3D)); 2) to compare MVA(3D) with conventional techniques: 2-dimensional (2D) planimetry (MVA(2D)), pressure half-time (MVA(PHT)), and continuity equation (MVA(CON)); and 3) to evaluate the degree of mitral commissural fusion. BACKGROUND 3DTEE is a novel technique that provides excellent image quality of the mitral valve. Real-time 3DTEE is a relatively recent enhancement of this technique. To date, there have been no feasibility studies investigating the utility of real-time 3DTEE in the assessment of RhMS. METHODS Forty-three consecutive patients referred for echocardiographic evaluation of RhMS and suitability for percutaneous mitral valvuloplasty were assessed using 2D transthoracic echocardiography and real-time 3DTEE. MVA(3D), MVA(2D), MVA(PHT), MVA(CON), and the degree of commissural fusion were evaluated. RESULTS MVA(3D) assessment was possible in 41 patients (95%). MVA(3D) measurements were significantly lower compared with MVA(2D) (mean difference: -0.16 ± 0.22; n=25, p<0.005) and MVA(PHT) (mean difference: -0.23 ± 0.28 cm(2); n=39, p<0.0001) but marginally greater than MVA(CON) (mean difference: 0.05 ± 0.22 cm(2); n=24, p=0.82). MVA(3D) demonstrated best agreement with MVA(CON) (intraclass correlation coefficient [ICC] 0.83), followed by MVA(2D) (ICC 0.79) and MVA(PHT) (ICC 0.58). Interobserver and intraobserver agreement was excellent for MVA(3D), with ICCs of 0.93 and 0.96, respectively. Excellent commissural evaluation was possible in all patients using 3DTEE. Compared with 3DTEE, underestimation of the degree of commissural fusion using 2D transthoracic echocardiography was observed in 19%, with weak agreement between methods (κ<0.4). CONCLUSIONS MVA planimetry is feasible in the majority of patients with RhMS using 3DTEE, with excellent reproducibility, and compares favorably with established methods. Three-dimensional transesophageal echocardiography allows excellent assessment of commissural fusion.

The Frequency of a Common Mutation of the Methionine Synthase Gene in the Australian Population and its Relation to Smoking and Coronary Artery Disease

Background Modest elevations in levels of circulating homocysteine are common in patients with vascular disease. Methionine synthase is a vitamin B12-dependent enzyme catalysing the re-methylation of homocysteine to methionine; reduced methionine synthase activity results in elevated level of homocysteine. Design A case-control study. Methods We explored the frequency and distribution of a 2756A → G (D919G) mutation of the methionine synthase gene, detected by polymerase chain reaction genotyping, in 745 Australian Caucasian patients aged ≤ 65 years (550 men and 195 women) with and without angiographically documented coronary artery disease (CAD). Results The frequency distributions of AA, A6 and GG genotypes were 61.9%, 33.8% and 4.3%, respectively, and were in Hardy-Weinberg equilibrium. There was no correlation between the methionine synthase mutation and CAD from simple χ2 comparison. However, the interactive term of life-time smoking dose with methionine synthase genotypes was predictive of both the number of significantly diseased vessels (≥50% luminal obstruction; χ2 = 12.518, P = 0.0019), and the presence or absence of significant CAD (χ2 = 7.045, P = 0.027). A stepwise logistic regression analysis showed that smokers who were also GG homozygotes had more severe CAD compared with smokers of other genotypes. The methionine synthase genotypes were not associated with any of the other established CAD risk factors assessed in our study. Conclusions We conclude that the methionine synthase 2756A → G mutation is common, with homozygosity occurring in approximately 4% of white Australians, and that it has an interactive effect with life-time smoking dose to increase the severity of CAD. Smokers who are also GG homozygotes have additionally elevated CAD risk.

Recurrent ischaemic mitral regurgitation post mitral annuloplasty due to suture dehiscence evaluated using real time three dimensional transoesophageal echocardiography.

Ischaemic mitral regurgitation after myocardial infarction results from geometric changes in left ventricular shape and displacement of papillary muscles with resultant tethering and incomplete leaflet coaptation of mitral leaflets. Post mitral valve repair, both valve apparatus related factors such as persistent leaflet tethering and progressive left ventricular adverse remodelling and procedure related factors such as ring dehiscence are important causes of recurrent mitral regurgitation after initial undersized mitral ring annuloplasty. Three-dimensional echocardiography is a novel clinical tool that has the potential to provide additional anatomical and functional information regarding the mechanism of recurrent mitral regurgitation post mitral valve repair that is complementary to standard two dimensional transoesophageal echocardiography thus helping guide the most appropriate subsequent therapeutic intervention.

Patent Foramen Ovale Influences the Presentation of Decompression Illness in SCUBA Divers

BACKGROUND Few have examined the influence of patent foramen ovale (PFO) on the phenotype of decompression illness (DCI) in affected divers. METHODOLOGY A retrospective review of our database was performed for 75 SCUBA divers over a 10-year period. RESULTS Overall 4,945 bubble studies were performed at our institution during the study period. Divers with DCI were more likely to have positive bubble studies than other indications (p<0.001). Major DCI was observed significantly more commonly in divers with PFO than those without (18/1,000 v.s. 3/1,000, p=0.02). Divers affected by DCI were also more likely to require a longer course of hyperbaric oxygen therapy (HBOT) if PFO was present (p=0.038). If the patient experienced one or more major DCI symptoms, the odds ratio of PFO being present on a transoesophageal echocardiogram was 3.2 (p=0.02) compared to those who reported no major DCI symptoms. CONCLUSION PFO is highly prevalent in selected SCUBA divers with DCI, and is associated with a more severe DCI phenotype and longer duration of HBOT. Patients with unexpected DCI with one or more major DCI symptoms should be offered PFO screening if they choose to continue diving, as it may have considerable prognostic and therapeutic implications.

Spontaneous splenic rupture due to rivaroxaban

In the prevention and treatment of thromboembolic disease, novel oral anticoagulants have emerged as alternatives to warfarin. A major challenge continues to be the reversal of their anticoagulant effect in the case of life-threatening haemorrhagic complications. We report a case of spontaneous splenic rupture treated by splenic artery embolisation in a 77-year-old woman who was anticoagulated with rivaroxaban.

Functional mitral valve regurgitation: repair or replacement?

rimary mitral valve disease involves damage to leaflet or chordal tissue, whereas functional P (or secondary) mitral regurgitation (MR) typically involves a combination of mitral annular dilatation and leaflet restriction caused by ventricular dysfunction in patients with normal leaflets and chordae. Assessing the severity of regurgitation in secondary MR is more difficult than in primary MR, as the regurgitant orifice area is often underestimated by echocardiography because of its crescent shape during systole. Left ventricular stroke volume is usually reduced in secondary MR, so that lesser degrees of regurgitant volume are more significant.

TCT-526 The Index of Microvascular Resistance Predicts Immediate Recovery of Left Ventricular Systolic Function Following PCI in Patients with NSTEACS

Coronary microvascular dysfunction has been shown to prognosticate patients with STEMI following primary PCI. Its role in patients with NSTEACS however has not been thoroughly investigated. This study aims to evaluate the relationship between Index of Microvascular Resistance (IMR) and acute

Operative Outcomes with Myxomatous Mitral Valve Repair: Experience with 586 Patients

INTRODUCTION American Heart Association (AHA) guidelines recommend mitral valve repair for myxomatous mitral regurgitation whenever possible to prevent LV dysfunction and early mortality. Here we review our early operative outcomes with mitral valve repair for myxomatous mitral regurgitation. METHODS We collected data from 586 consecutive patients that underwent mitral repair for myxomatous disease at the Prince Henry and Prince of Wales Hospitals Sydney between 1997 and 2012. All patients had pre- and postoperative transthoracic echocardiograms. RESULTS In the first 30 days postoperatively there were five deaths (0.9%), four strokes (0.7%) and five transient ischaemic attacks (TIAs) (0.9%). Repair involved resection in 55.5%, neochordal reconstruction in 41.6%, and in 2.9% a combination of both. There was increasing use of neochordae since 2006. At discharge 99% had mitral regurgitation (MR) ≤ mild and ≤ trivial in 79.5%. For posterior leaflet disease neochordae had improved MR at discharge compared with resection (85% vs 78%, P<0.05). Preoperative triscupid regurgitation (TR) and pulmonary hypertension > mild were associated with a greater degree of MR at discharge (P<0.05) for reasons that are unclear. CONCLUSION We have shown excellent early results for mitral repair with very low operative mortality and excellent freedom from significant MR. Successful mitral repairs with low morbidity have resulted in a pattern of early referral in keeping with the current guidelines.