Background and aim of the study: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a three-month administration of warfarin following bioprosthetic valve replacement (BVR). However, strong evidence supporting this recommendation is lacking, making process variation likely.

Methods: In the ANSWER Registry, a total of 386 patients who had received either Epic or Biocor BVRs between May 2007 and August 2008 at 40 centers was enrolled. Patterns of discharge anticoagulation and outpatient International Normalized Ratio (INR) values were collected. Mortality, embolic, and bleeding events were assessed up to six months after BVR.

Results: The median patient age was 74 years (interquartile range (IQR): 67-80 years), 39% of patients were female, and 65% were classified as a high thromboembolic risk. Warfarin was prescribed in 38% of all BVR patients, and in 49% of those at high risk of thromboembolism. The median time to therapeutic INR was nine days (IQR: 1 to 18 days), and 20% of patients failed to reach therapeutic levels. Among those patients achieving a therapeutic INR, 78% and 57% respectively had at least one subtherapeutic or supratherapeutic INR during the subsequent follow up to three months. During the follow up, patients treated with warfarin had similar rates of embolic events (2.8% versus 3.1%, p = 0.884), but a substantially higher incidence of bleeding than those not treated with warfarin (12% versus 3%, p = 0.0012). Among patients who were anticoagulated, those with supratherapeutic INR-values had a seven-fold higher risk for overt bleeding events (26% versus 3%).

Conclusion: Anticoagulation strategies after BVR are highly variable. In this population, challenges in achieving and maintaining therapeutic warfarin anticoagulation are common, and are associated with an increased risk of bleeding. Further studies are required to clarify the optimal post-BVR anticoagulation strategy.

Background and aim of the study: Aortic regurgitation (AR) is a disease for which there is currently no effective medical treatment. It has been shown previously in an experimental model of AR that the renin-angiotensin-aldosterone system (RAAS) plays a major role, and that medications blocking the RAAS are effective to protect against left ventricular (LV) hypertrophy and also help to maintain a normal systolic function. The role of aldosterone receptor blockers in this disease has never been evaluated. Thus, the effects were studied of the aldosterone receptor blocking agent spironolactone in a model of chronic AR in rats.

Methods: The effects of a six-month treatment with spironolactone were evaluated in adult Wistar rats with severe AR, compared to sham-operated and untreated AR animals.

Results: Spironolactone treatment decreased the total heart weight. In addition, the LV expression of atrial natriuretic peptide mRNA was decreased by spironolactone treatment, as was the expression of collagen 1 and LOX1 mRNAs. Left ventricular fibrosis was decreased by spironolactone treatment.

Conclusion: Spironolactone protected against volume-overload cardiomyopathy in this model of aortic valve regurgitation. The predominant protective effect was a decrease in myocardial fibrosis.

Background and aim of the study: Aortic valve stenosis (AS) is an important cardiovascular disease that affects between 2% and 7% of the elderly population in industrialized countries. AS often coexists with asymmetric septal hypertrophy (ASH), which is generally caused by a protrusion of the hypertrophied left ventricular outflow tract (LVOT) just below the aortic valve. The study aim was to determine, based on measurement of the aortic valve effective orifice area (EOA), if ASH might potentially interfere with the assessment of AS severity.

Methods: The effects of different levels of ASH (from normal to 90%) on the EOA measured from orifices mimicking different AS severities, and from a home-built AS model constructed from a bioprosthetic aortic valve, were examined in a pulsatile flow in-vitro model.

Results: For the most severe AS, the level of ASH had no impact on the measured EOA. In contrast, for the less severe AS, beyond an ASH level of 50% the AS severity was progressively overestimated, and reached a reduction of about 60% of EOA for a ASH level of 90%.

Conclusion: The presence of concomitant ASH may cause an overestimation of the hemodynamic severity of AS. The extent of overestimation is more important in less-severe AS. Hence, the presence of ASH may lead the clinician to conclude, erroneously, that the AS is severe and that aortic valve replacement is indicated. However, beyond an ASH level of 50% the AS severity can be accurately determined.

Background and aim of the study: Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR).

Methods: A total of 35 patients undergoing elective surgical AVR under cardiopulmonary bypass was enrolled in the study. Intraoperative RT-3D TEE was used prospectively to acquire volumetric echocardiographic datasets immediately before and after AVR. The 3D echocardiographic data were analyzed offline using TomTec Mitral Valve Assessment software to assess changes in specific mitral annular geometric parameters.

Results: Datasets were successfully acquired and analyzed for all patients. A significant reduction was noted in the mitral annular area (-16.3%, p < 0.001), circumference (-8.9%, p < 0.001) and the anteroposterior (-6.3%, p = 0.019) and anterolateral-posteromedial (-10.5%, p < 0.001) diameters. A greater reduction was noted in the anterior annulus length compared to the posterior annulus length (10.5% versus 6.2%, p < 0.05) after AVR. No significant change was seen in the non-planarity angle, coaptation depth, and closure line length. During the period of data acquisition before and after AVR, no significant change was noted in the central venous pressure or left ventricular end-diastolic diameter.

Conclusion: The mitral annulus undergoes significant geometric changes immediately after AVR. Notably, a 16.3% reduction was observed in the mitral annular area. The anterior annulus underwent a greater reduction in length compared to the posterior annulus, which suggested the existence of a mechanical compression by the prosthetic valve.

Background and aim of the study: Calcific aortic valve stenosis (AS) affects 2-5% of the population aged > 65 years. Functional DNA variants at the NOTCH1 locus result in bicuspid aortic valve (BAV) and severe valve calcification. The contribution of these variants to AS in the population with tricuspid aortic valve (TAV) remains to be determined.

Methods: Fourteen genetic variants surrounding the NOTCH1 gene were genotyped, including rare mutations previously reported, and common polymorphisms. The study involved 457 French Canadian patients with severe tricuspid AS. Genotyping was carried out using the Illumina BeadXpress platform. Allele frequencies of common single nucleotide polymorphisms (SNPs) for patients with AS were compared to a shared control group of European ancestry (n = 3,294). In total, 88 ancestry-informative markers were used to correct for population stratification.

Results: The mutation R1107X, previously associated with AS and BAV, was identified in a relatively young patient (aged 58 years). The mutations R1279H and V2285I were detected in 18 and 14 heterozygotes, respectively. A common polymorphism (rs13290979) located in intron 2 was significantly associated with AS (p = 0.003), which remained significant after correction for multiple testing. However, this association was no longer significant after accounting for population stratification (p = 0.088).

Conclusion: In this study, rare functional variants were found in the NOTCH1 gene in a French Canadian population of patients with severe tricuspid AS. This also suggests, for the first time, the presence of a common polymorphism in this gene conferring susceptibility to AS.