Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

OBJECTIVE: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). METHODS: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. RESULTS: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. CONCLUSIONS: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice.

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Prognostic Implications of Raphe in Bicuspid Aortic Valve Anatomy.

Importance: Little is known about the association between bicuspid aortic valve (BAV) morphologic findings and the degree of valvular dysfunction, presence of aortopathy, and complications, including aortic valve surgery, aortic dissection, and all-cause mortality. Objective: To investigate the association between BAV morphologic findings (raphe vs nonraphe) and the degree of valve dysfunction, presence of aortopathy, and prognosis (including need for aortic valve surgery, aortic dissection, and all-cause mortality). Design, Setting, and Participants: In this large international multicenter registry of patients with BAV treated at tertiary referral centers, 2118 patients with BAV were evaluated. Patients referred for echocardiography from June 1, 1991, through November 31, 2015, were included in the study. Exposures: Clinical and echocardiographic data were analyzed retrospectively. The morphologic BAV findings were categorized according to the Sievers and Schmidtke classification. Aortic valve function was divided into normal, regurgitation, or stenosis. Patterns of BAV aortopathy included the following: type 1, dilation of the ascending aorta and aortic root; type 2, isolated dilation of the ascending aorta; and type 3, isolated dilation of the sinus of Valsalva and/or sinotubular junction. Main Outcomes and Measures: Association between the presence and location of raphe and the risk of significant (moderate and severe) aortic valve dysfunction and aortic dilation and/or dissection. Results: Of the 2118 patients (mean [SD] age, 47 [18] years; 1525 [72.0%] male), 1881 (88.8%) had BAV with fusion raphe, whereas 237 (11.2%) had BAV without raphe. Bicuspid aortic valves with raphe had a significantly higher prevalence of valve dysfunction, with a significantly higher frequency of aortic regurgitation (622 [33.1%] vs 57 [24.1%], P < .001) and aortic stenosis (728 [38.7%] vs 51 [21.5%], P < .001). Furthermore, aortic valve replacement event rates were significantly higher among patients with BAV with raphe (364 [19.9%] at 1 year, 393 [21.4%] at 2 years, and 447 [24.4%] at 5 years) vs patients without raphe (30 [14.0%] at 1 year, 32 [15.0%] at 2 years, and 40 [18.0%] at 5 years) (P = .02). In addition, the all-cause mortality event rates were significantly higher among patients with BAV with raphe (77 [5.1%] at 1 year, 87 [6.2%] at 2 years, and 110 [9.5%] at 5 years) vs patients without raphe (2 [1.8%] at 1 year, 3 [3.0%] at 2 years, and 5 [4.4%] at 5 years) (P = .03). However, on multivariable analysis, the presence of raphe was not significantly associated with all-cause mortality. Conclusions and Relevance: In this large multicenter, international BAV registry, the presence of raphe was associated with a higher prevalence of significant aortic stenosis and regurgitation. The presence of raphe was also associated with increased rates of aortic valve and aortic surgery. Although patients with BAV and raphe had higher mortality rates than patients without, the presence of a raphe was not independently associated with increased all-cause mortality.

Transcatheter Valve-in-Valve: A Cautionary Tale.

Transcatheter aortic valve replacement (TAVR) by valve-in-valve (VIV) implantation is an alternative treatment for high-risk patients with a degenerating aortic bioprosthesis. We present a case of transapical TAVR VIV with a 29-mm Edwards SAPIEN XT (ESV) (Edwards Lifesciences, Irvine, CA) into a 29-mm Medtronic Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, MN) in which unanticipated dilatation of the Freestyle bioprosthesis resulted in intraprocedural embolization of the TAVR valve, necessitating urgent conversion to a conventional surgical aortic valve replacement (AVR). Our experience suggests that TAVR VIV with the 29-mm ESV in the setting of a degenerated 29-mm Freestyle stentless bioprosthesis must be undertaken with caution.

Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden. Anderson-Fabry disease is an X-linked disorder, and genetic testing is critical for the diagnosis of AFD in women. Echocardiography with strain imaging and cardiac magnetic resonance imaging using late enhancement and T1 mapping are important imaging tools. The current therapy for AFD is enzyme replacement therapy (ERT), which can reverse or prevent AFD progression, while gene therapy and the use of molecular chaperones represent promising novel therapies for AFD. Anderson-Fabry cardiomyopathy is an important and potentially reversible cause of heart failure that involves LVH, increased susceptibility to arrhythmias and valvular regurgitation. Genetic testing and cardiac MRI are important diagnostic tools, and AFD cardiomyopathy is treatable if ERT is introduced early.

Canadian Cardiovascular Society guidelines on the use of cardiac resynchronization therapy: implementation.

Recent studies have provided the impetus to update the recommendations for cardiac resynchronization therapy (CRT). This article provides guidance on the implementation of CRT and is intended to serve as a framework for the implementation of CRT within the Canadian health care system and beyond. These guidelines were developed through a critical evaluation of the existing literature, and expert consensus. The panel unanimously adopted each recommendation. The 9 recommendations relate to patient selection in the presence of comorbidities, delivery and optimization of CRT, and resources required to deliver this therapy. The strength of evidence was weighed, taking full consideration of any risk of bias, and any imprecision, inconsistency, and indirectness of the available data. The strength of each recommendation and the quality of evidence were adjudicated. Trade-offs between desirable and undesirable consequences of alternative management strategies were considered, as were values, preferences, and resource availability. These guidelines were externally reviewed by experts, modified based on those reviews, and will be updated as new knowledge is acquired.

Systolic and diastolic function assessment in fabry disease patients using speckle-tracking imaging and comparison with conventional echocardiographic measurements.

BACKGROUND: Fabry cardiomyopathy is characterized by progressive left ventricular hypertrophy (LVH) associated with diastolic dysfunction and is the most common cause of death in Fabry disease (FD). However, LVH is not present in all subjects, particularly early in disease progression and in female patients. Direct assessment of myocardial deformation by strain and strain rate (SR) analysis may be sensitive to detect subclinical Fabry cardiomyopathy independent of the presence of LVH. METHODS: Systolic (longitudinal, circumferential, and radial systolic strain and SR) and diastolic (SR during isovolumic relaxation [SR(IVR)] and early diastole and strain at peak transmitral E wave) function was assessed in 16 patients with FD using two-dimensional speckle-tracking echocardiography. In addition, mean S' and E' mitral annular velocities by Doppler tissue imaging were measured. Diastolic filling indices, including E/SR(IVR) and E/E' ratios, were calculated. The patients were compared with 24 healthy age-matched and gender-matched controls. RESULTS: All 16 patients with FD had normal left ventricular ejection fractions, and nine patients had LVH. Compared with controls, patients with FD had reduced longitudinal systolic strain (P < .001) and systolic SR (P = .007), while there were no differences in circumferential systolic strain and S'. Diastolic function assessment showed reduced longitudinal early diastolic SR (P = .001), SR(IVR) (P < .001), and E/SR(IVR) (P < .001), while radial and circumferential diastolic function was not affected. Of the conventional diastolic function indices, reductions were seen in E (P = .006), E' (P = .021), and E/E' ratio (P < .001). After correcting for LVH, only SR(IVR) (P < .001) and E/SR(IVR) (P = .025) remained significantly different between patients with FD and controls, with sensitivity of 94% and specificity of 92% for SR(IVR) of 0.235 sec(-1) (area under the receiver operating characteristic curve, 0.953). CONCLUSIONS: Strain and SR analysis is useful in identifying patients with FD with reduced myocardial function, with longitudinal systolic strain and diastolic isovolumic SR being superior to the other echocardiographic measurements of myocardial contraction and relaxation and independent of LVH.

T1 mapping with cardiovascular MRI is highly sensitive for Fabry disease independent of hypertrophy and sex.

BACKGROUND: Fabry disease (FD) is an X-linked disorder of lysosomal metabolism affecting multiple organs with cardiac disease being the leading cause of death. Current imaging evaluations of the heart are suboptimal. The goals of the current study are to evaluate the potential of quantitative T1 mapping with cardiovascular MRI as a disease-specific imaging biomarker. METHODS AND RESULTS: A total of 31 patients with FD, 23 healthy controls, and 21 subjects with concentric remodeling or hypertrophy underwent cardiovascular MRI to measure left ventricular (LV) morphology, function, delayed enhancement, as well as myocardial T1 values, and derived parameters (extracellular volume). All subjects had LV ejection fraction >50% and similar volumes. FD and concentric remodeling or hypertrophy had similarly increased mass, wall thickness, and mass/volume as compared with controls. A total of 16 of 31 FD subjects and 10 of 21 concentric remodeling or hypertrophy subjects had LV hypertrophy. Noncontrast myocardial T1 values were substantially lower in FD as compared with controls and concentric remodeling or hypertrophy (1070 ± 50, 1177 ± 27, and 1207 ± 33 ms, respectively; P<0.001), but extracellular volume was similar in all groups (21.7 ± 2.4%, 22.2 ± 3.1%, and 21.8 ± 3.9%, respectively). Single-voxel NMR spectroscopy in 4 FD and 4 healthy control subjects showed a significant negative linear relationship between lipid content and noncontrast T1 values (r=-0.9; P=0.002). Female subjects had lower LV mass and wall thickness, longer myocardial T1 values and larger extracellular volume suggesting a key sex difference in cardiac remodeling. CONCLUSIONS: Reduced noncontrast myocardial T1 values are the most sensitive and specific cardiovascular MRI parameter in patients with FD irrespective of sex and LV morphology and function.

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans.

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Automated assessment of the aortic root dimensions with multidetector row computed tomography.

BACKGROUND: Accurate aortic root measurements and evaluation of spatial relationships with coronary ostia are crucial in preoperative transcatheter aortic valve implantation assessments. Standardization of measurements may increase intraobserver and interobserver reproducibility to promote procedural success rate and reduce the frequency of procedurally related complications. This study evaluated the accuracy and reproducibility of a novel automated multidetector row computed tomography (MDCT) imaging postprocessing software, 3mensio Valves (version 4.1.sp1, Medical Imaging BV, Bilthoven, The Netherlands), in the assessment of patients with severe aortic stenosis candidates for transcatheter aortic valve implantation. METHODS: Ninety patients with aortic valve disease were evaluated with 64-row and 320-row MDCT. Aortic valve annular size, aortic root dimensions, and height of the coronary ostia relative to the aortic valve annular plane were measured with the 3mensio Valves software. The measurements were compared with those obtained manually by the Vitrea2 software (Vital Images, Minneapolis, MN). RESULTS: Assessment of aortic valve annulus and aortic root dimensions were feasible in all the patients using the automated 3mensio Valves software. There were excellent agreements with minimal bias between automated and manual MDCT measurements as demonstrated by Bland-Altman analysis and intraclass correlation coefficients ranging from 0.97 to 0.99. The automated 3mensio Valves software had better interobserver reproducibility and required less image postprocessing time than manual assessment. CONCLUSIONS: Novel automated MDCT postprocessing imaging software (3mensio Valves) permits reliable, reproducible, and automated assessments of the aortic root dimensions and spatial relations with the surrounding structures. This has important clinical implications for preoperative assessments of patients undergoing transcatheter aortic valve implantation.

Mitral valve morphology assessment: three-dimensional transesophageal echocardiography versus computed tomography.

BACKGROUND: Advances in the minimally invasive mitral valve repair techniques increase the demands on accurate and reliable morphologic assessment of the mitral valve using three-dimensional imaging modalities. The present study compared mitral valve geometry measurements obtained by three-dimensional transesophageal echocardiography (TEE) to those obtained with multidetector row computed tomography (MDCT) used as a standard reference. METHODS: Clinical preoperative MDCT and intraoperative three-dimensional TEE were performed in 43 patients (mean age 81.0 ± 7.7 years) considered for transcatheter valve implantation procedure. Various measurements of mitral valve geometry were obtained from three-dimensional TEE datasets using mitral valve quantification software, and compared with those obtained from MDCT images using multiplanar reformation planes. RESULTS: Moderate and severe mitral regurgitation was present in 48.9% of patients. There was good agreement in mitral valve geometry measurements between three-dimensional TEE and MDCT without significant overestimation or underestimation and tight 95% limits of agreement. For linear dimensions, angles and areas, the 95% limits of agreement were less than 1 cm, less than 15 degrees, and less than 2 cm(2), respectively. In addition, the intraclass correlation coefficients were more than 0.8 for all parameters. Finally, the measurements were highly reproducible, with low intraobserver and interobserver variability (nonsignificant overestimation or underestimation and narrow 95% limits of agreement). CONCLUSIONS: The present study demonstrates the accuracy and clinical feasibility of the assessment of the mitral valve geometry with three-dimensional TEE that is comparable to the MDCT measurements. Three-dimensional TEE and MDCT provide accurate and complementary information in the evaluation of patients with mitral valve disease. Its potential incremental clinical value in the field of transcatheter mitral repair procedures needs further assessment in the future studies.

Longitudinal mechanics of the periinfarct zone and ventricular tachycardia inducibility in patients with chronic ischemic cardiomyopathy.

BACKGROUND: Quantification of segmental left ventricular (LV) strain by speckle-tracking echocardiography can identify transmural infarcts in patients with chronic ischemic cardiomyopathy. The aim of the study was to explore the relationship between the LV longitudinal peak systolic strain (LPSS) of the infarct, periinfarct, and remote zones and monomorphic ventricular tachycardia (VT) inducibility on electrophysiologic (EP) study. METHODS: A total of 134 patients with chronic ischemic cardiomyopathy scheduled for EP study were included. The protocol consisted of clinical, electrocardiographic, and echocardiographic evaluation, including LV longitudinal strain analysis using speckle-tracking echocardiography, immediately before EP study. An infarct segment was defined as a longitudinal strain value of greater than -5%, and a periinfarct segment was defined as immediately adjacent to an infarct segment. RESULTS: The infarct zone had the most impaired longitudinal strain (-0.5% ± 3.0%), whereas the periinfarct and remote zones had more preserved longitudinal strain (-10.8% ± 1.9% and -14.5% ± 3.0%, respectively; analysis of variance, P < .001). Seventy-two (54%) patients had inducible monomorphic VT on EP study. There was no significant difference in LV ejection fraction (31% ± 9% vs 32% ± 11%, P = .29) between inducible and noninducible patients. Longitudinal peak systolic strain of the periinfarct zone was more impaired in inducible patients (-9.8% ± 1.5% vs -11.0% ± 2.1%, P = .001), but no differences in LPSS of the infarct (-0.5% ± 3.2% vs -0.4% ± 2.7%, P = .75) and remote (-14.6% ± 2.8% vs -14.5% ± 3.4%, P = .92) zones were observed. Only LPSS of the periinfarct zone (OR 1.43, 95% CI 1.15-1.78, P = .001) was independently related to monomorphic VT inducibility on multiple logistic regression. CONCLUSIONS: Longitudinal strain analysis may be a useful imaging tool to risk stratify ischemic patients for malignant ventricular arrhythmia.

Churg-Strauss syndrome with myocarditis manifesting as acute myocardial infarction with cardiogenic shock: case report and review of the literature.

A patient with a two-year history of worsening asthma presented with chest pain and shortness of breath. She developed cardiogenic shock. Analysis of blood chemistry detected increased troponin I concentration. Her electrocardiographic changes were consistent with a diagnosis of anteroseptal myocardial infarction. However, angiography showed normal coronary arteries. Left ventriculography showed severe mitral regurgitation and global hypokinesis. Peripheral eosinophilia was detected. Subsequent endomyocardial biopsy showed myocarditis with prominent eosinophil and plasma cell components. Churg-Strauss syndrome was diagnosed based on her history of asthma, evidence of peripheral eosinophilia and results of endomycardial biopsy. Treatment with a high dose of corticosteroids was initiated. As symptoms of heart failure improved - without recurrence of cardiac and respiratory symptoms - the dose of corticosteroids was gradually reduced. Eight months after her original presentation, she developed urticarial lesions on her abdomen and legs, with muscle soreness but no other associated symptoms. She was treated with a combination of prednisone and dapsone. After the diagnosis of Churg-Strauss syndrome, the patient remained symptom free with a normal ejection fraction for 15 months while taking prednisone.