Browsing by Author "Lahmers, Sunshine M."
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- Accuracy of Noninvasively Determined Pulmonary Artery Pressure in Dogs With Myxomatous Mitral Valve DiseaseMenciotti, Giulio (Virginia Tech, 2020-07-23)Development of pulmonary hypertension is an independent predictor of poor outcome in dogs affected by myxomatous valvular degeneration (MMVD). Systolic pulmonary arterial pressure is routinely estimated by Doppler echocardiography applying the simplified Bernoulli equation to the velocity of tricuspid regurgitation (sPAP_D). The accuracy of this estimation is unknown in dogs with MMVD, but experimental studies suggest that the method is imperfect. In order to fill this knowledge gap we prospectively enrolled dogs affected by MMVD and cardiac remodeling - American College of Veterinary Internal Medicine (ACVIM) stages B2 and C MMVD for which treatment had been unchanged for at least one month. A flow-directed thermodilution monitoring catheter was percutaneously placed in the right jugular vein and advanced to the main pulmonary artery. Pulmonary arterial systolic pressure was recorded through this catheter connected to a pressure-transducer and data acquisition-analysis system (sPAP_C). A second operator simultaneously acquired tricuspid regurgitant velocity spectra to calculate sPAP_D. Each operator was blinded to the result of the other technique. Twenty dogs were enrolled. Technical difficulties prevented catheterization in 2 dogs. Eighteen measurement pairs were therefore used for comparison of sPAP_C and sPAP_D through Bland-Altman analysis and linear regression. A statistically significant bias between sPAP_C and sPAP_D (mean difference=0.5mmHg; Confidence interval: -6.5mmHg, +7.5mmHg) was not detected. The limits of agreement between the techniques were wide (-27.3mmHg, +28.2mmHg). Regression analysis failed to identify a significant linear association between the two techniques (r=0.11, p=0.17). In conclusion, sPAP_D poorly agrees with sPAP_C measurement in dogs affected by MMVD in ACVIM stages B2 and C. In these dogs, sPAP_D could under- or over-estimate sPAP_C by more than 20mmHg, and therefore caution should be used when interpreting PASP_D.
- Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiographyMenciotti, Giulio; Borgarelli, Michele; Aherne, Michael; Camacho, Paula; Haggstrom, Jens; Ljungvall, Ingrid; Lahmers, Sunshine M.; Abbott, Jonathan A. (Wiley, 2018-09-01)Background: Myxomatous mitral valve disease (MMVD) is more prevalent in Cavalier King Charles Spaniels (CKCSs) compared to dogs of other breeds at a given age. Abnormal valvular stress is thought to contribute to the development and progression of MMVD, and a relationship exists between mitral valve (MV) morphology and stress acting on the valve. Objectives: To determine whether the MV morphology of healthy adult CKCSs differs from the morphology of healthy adult dogs of other breeds determined by RT-3DTTE. Animals: Thirty-five healthy CKCSs and 41 healthy dogs of other breeds. Methods: Prospective cross-sectional study. Dogs underwent physical examination, conventional echocardiography, and RT-3DTTE. RT–3DTTE datasets were analyzed using dedicated software for MV morphologic analysis. Morphologic variables were compared between CKCSs and dogs of other breeds. Results: The MV of healthy CKCSs had a smaller annulus height (0.46 ± 0.11 vs. 0.56 ± 0.17; P =.0021), tenting height (0.26 ± 0.12 vs. 0.42 ± 0.18; P <.001), tenting area (0.42 ± 0.15 vs. 0.79 ± 0.34; P <.001), normalized tenting volume (0.09 [0.05–0.13] vs. 0.14 [0.10–0.20]; P <.001), and normalized area of the posterior leaflet (0.57 ± 0.15 vs. 0.66 ± 0.18; P =.016) compared to healthy dogs of other breeds; this results in CKCSs having a flatter MV with reduced tenting, compared to the MV of other breeds. Conclusions and Clinical Importance: These morphologic features could confer a mechanical disadvantage and play a role in the predisposition of CKCSs to the early development of MMVD.
- Evaluation of right ventricular function using conventional and real-time 3-dimensional echocardiography in normal dogs and dogs with myxomatous mitral valve diseaseAherne, Michael (Virginia Tech, 2017-06-06)Objectives: To investigate the feasibility of real-time three-dimensional (3D) echocardiographic analysis of right ventricular (RV) function in healthy dogs and to compare conventional and 3D echocardiographic (3DE) indices of RV function in dogs with various stages of myxomatous mitral valve disease (MMVD), classified per the guidelines of the American College of Veterinary Internal Medicine, to those from healthy dogs. Animals: Twenty-two healthy dogs and 56 dogs with MMVD Methods: All dogs underwent conventional and 3D echocardiographic examinations. Measurements of 3DE RV function indices including RV end-diastolic volume (EDV), RV end-systolic volume (ESV), RV stroke volume (SV), and RV ejection fraction (EF) were recorded. Measurements of conventional indices of RV function were also obtained. RV EDV, ESV, and SV were indexed to bodyweight (BW) and analyzed using commercially available software. Results: Three-dimensional RV datasets could be acquired and analyzed in all dogs. Intra- and inter-observer coefficents of variation were > 20% for all 3D RV indices. Right ventricular EDV and ESV were decreased and RV EF was increased in dogs with advanced MMVD when compared to controls. Several conventional echocardiographic indices of RV function also differed between the control group and various MMVD groups. Conclusions: Real-time 3DE RV assessment is feasible in normal dogs with acceptable intra- and inter-observer variability. Several 3DE indices of RV systolic function differ between dogs with advanced MMVD when compared to normal dogs. Further investigation is required to determine if these differences have clinical implications.
- Investigating the coordination of cardiac conduction and repolarization in ventricular myocardiumBlair, Grace Anna (Virginia Tech, 2023-07-27)Aberrations in conduction or repolarization are established prerequisites for arrhythmogenesis. The following dissertation investigates how reducing either ephaptic (EpC) or gap junctional (GJ) coupling between cardiomyocytes can modulate cardiac conduction, repolarization, or the relationship between these two phenomena. Our lab has previously demonstrated that EpC can be modified in the ventricular epicardium using ionic and osmotic challenges to the Langendorff-perfused heart. In the first series of experiments, we show that reducing EpC via treatment with mannitol or hyponatremia can unmask conduction deficits that are otherwise below the resolution of detection in Scn5a+/- mice. Interestingly, we also observe that combination of the two treatments resolves severe conduction delay due to hyponatremia in the heterozygous animal. These data suggest it may be valuable to pursue the use of mannitol or hyponatremia as novel diagnostics for sodium channel loss of function diseases. The importance of extracellular perfusate is also highlighted by the second investigation, which evaluates how sodium and calcium concentration modulate repolarization in the context of hyperkalemia, a common comorbidity of hospitalized patients that increases the risk of arrhythmia. Calcium may potentially play a role in modulating APD adaptation to pacing rate in the context of this disease state, though more research is needed to clarify the exact mechanism of this effect. Finally, we investigate the relationship between conduction and repolarization in the epicardium, and conclude that this relationship does not appear to be dictated by the degree of cell-cell coupling in the myocardium, but instead is driven by endogenous gradients of action potential duration within the tissue. Taken together, these data demonstrate ways in which both conduction and repolarization are sensitive to modulations of EpC, though we also find that the relationship between these two phenomena is not influenced by such changes in electrical coupling.
- The longitudinal outcome of canine myxomatous mitral valve disease in dogs: The LOOK Mitral studyFranchini, Alessandra (Virginia Tech, 2022-06-07)Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. However, prospectively acquired data describing the natural history and prognostic factors in a large population of dogs affected by this disease are sparse. Thus, the Longitudinal Outcome of canine (K9) myxomatous mitral valve disease registry (LOOKmitral) was established to prospectively collect clinical and diagnostic data from a large population of dogs affected by MMVD. A total of 6,102 dogs were enrolled in the LOOK-mitral registry from November 1st, 2015, to October 31st, 2018, in thirteen cardiology specialty practices. We first described the baseline characteristics of the dogs enrolled in the registry, which mainly confirmed previous findings. Moreover, we provided new additional results, such as the presence of systolic dysfunction in some small breed dogs and how the intensity of the murmur correlates with the severity of MMVD also in large breed dogs. Second, we described the baseline treatment characteristics at the time of enrollment. These data showed that the results of the "Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly" (EPIC) trial and left atrial and left ventricular dimensions, assessed by echocardiography, influenced veterinary cardiologist's prescription of cardiovascular drugs in affected dogs. Lastly, we evaluated predictors of reoccurrence of congestive signs within 180 days after successfully treating the first episodes of heart failure in dogs enrolled in the LOOKMitral registry. While this study failed to identify accurate predictors of recurrence, dogs with larger left ventricular internal dimensions at end-diastole were more likely to present with reoccurrence of clinical signs suggesting that closer monitoring of these dogs may be recommended.
- Performance of Different Echocardiographic Measurements of Left Atrial Size in Dogs by Observers with Different Levels of ExperienceSafian, Alexander M.; Menciotti, Giulio; Lahmers, Sunshine M.; Jeong, Hyeon; Franchini, Alessandra; Borgarelli, Michele (MDPI, 2022-03)Simple Summary Assessing enlargement of the left atrium (one of the four cardiac chambers) is extremely important for gaining information about dogs' heart disease, their prognosis, and directing treatment. However, people with different levels of experience may be required to make this assessment, and we don't know how observers with different experiences perform in making this assessment. In this study, five observers with different levels of experience evaluated the left atrium of 36 dogs in a blinded fashion (i.e., unaware of each other measurements, or of the identity of the dog), compared to two cardiologists. We then used statistical analysis to evaluate repeatability, reproducibility, accuracy of the measurements, and the capacity of correctly identifying left atrial enlargement. We found that the measurements performed by observers with more experience where more similar to the cardiologists' measurements, and that combining more than one technique for measuring the left atrium can improve accuracy of the identification of left atrial enlargement. Assessment of left atrial (LA) sizes in dogs informs clinical staging, risk assessment, treatment decisions, and prognosis. The objective of this study was to assess the diagnostic performance of observers with different levels of experience measuring the LA with three different techniques. Echocardiographic images from 36 dogs with different degrees of left atrial enlargement (LAE) were retrospectively retrieved, anonymized and measured in a blinded fashion by a veterinary student, a first-year cardiology resident, a third-year cardiology resident, and two board-certified veterinary cardiologists. The LA to aortic root ratio (LA:Ao), LA antero-postero diameter indexed to body weight (LAiAPD) and left atrial area were measured. Inter- and intra-observer intraclass correlation coefficients (ICCs) were calculated for all three variables. Bland-Altman plots and accuracy in identification of LAE were calculated for the three least experienced observers using LA:Ao and LAiAPD. Intra- and interobserver ICCs were greater than 0.9 for every variable. The observer with least experience had significant positive bias and a tendency to overestimate larger measurements using LA:Ao, but not using LAiAPD. The accuracy of identification of LAE also increased with the increasing level of experience and was higher for LAiAPD compared to LA:Ao. Combining both methods for identification of LAE, further increased accuracy.
- Sodium Channel Loss of Function Sensitizes Conduction to Changes in Extracellular Sodium ConcentrationAdams, William Patrick (Virginia Tech, 2024-06-04)Sudden cardiac death is largely attributable to sudden onset ventricular arrhythmias. Alterations in cardiac conduction, particularly the slowing of conduction velocity is one major factor in arrhythmogenesis. By understanding the mechanisms and factors that modulate cardiac conduction velocity, we can assess and perhaps mitigate the risk of arrhythmia in patients for whom slowed conduction is a arrhythmogenic substrate. Cardiac conduction has traditionally been described by cable theory, which predicts an inverse relationship between extracellular resistance and conduction velocity (CV). However, in studies that reduce extracellular resistance by inducing interstitial edema, there are conflicting results, with some labs showing increased CV when edema is induced with one agent, and others showing reduced CV when edema is induced with a different agent. In the first part of this dissertation, we present experimental data in support of ephaptic coupling (EpC), a theorized mechanism of conduction that resolves these apparent contradictions. In the later part of this dissertation, we address how changes in sodium concentration can alter conduction, despite conventional wisdom suggesting that it should not. We show that when sodium channels are impaired, such as by genetic mutation or pharmacologic blockade, that conduction is sensitized to changes in sodium concentrations that would not otherwise induce changes in CV. We go on to explore the mechanisms that modulate this sensitivity and present data that show it is a function of both EpC and outward potassium currents. Taken together, these data expand our understanding of the mechanics behind cardiac conduction and demonstrate that EpC has a clinically relevant impact on conduction and represents a new pathway to explore in regard to the treatment and management of arrhythmogenic and conduction disorders.