Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

Interruption of the tricuspid regurgitant jet: A possible consequence of reflected waves.

Reflected pressure waves can impact central aortic pressure, and can cause notching of the pulmonic valve Doppler signal. However, reflected waves in the venous system usually do not achieve a high enough velocity to alter Doppler flow patterns. Herein we report a case of systolic notching of the tricuspid regurgitant signal that likely resulted from reflected venous waves.

NAFLD in Cardiovascular Diseases: A Contributor or Comorbidity?

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.

Simultaneous transcatheter tricuspid and mitral valve-in-valve replacement for the treatment of degenerated bioprosthetic valves.

Transcatheter valve-in-valve replacement has become a viable option for patients with degenerated bioprosthetic valves at high risk for redo surgery. We report a case of a patient who had degenerated mitral and tricuspid bioprosthesis causing severe tricuspid and mitral regurgitation. We performed simultaneous mitral and tricuspid valve-in-valve replacement via a transfemoral approach. Although the data on performing both valve-in-valve procedures are limited, this case demonstrated that these procedures can be safely done as a single procedure.

Clinical correlates of hand-held ultrasound-guided assessments of the inferior vena cava in patients with acute decompensated heart failure.

BACKGROUND: Accurately assessing volume status in acutely decompensated heart failure (ADHF) can be challenging. Inferior vena cava (IVC) dynamics by echocardiography allow indirect assessment of volume status in these patients. Recently introduced hand-held ultrasound devices are promising. We aimed to describe the clinical correlates of volume status assessment using a hand-held ultrasound device in ADHF. METHODS: In this prospective study, we evaluated 106 patients admitted with ADHF. First scan was performed within 24 hours of admission and timed in reference to first dose of intravenous diuretic. Daily resting and inspiratory (sniff) IVC diameters were measured according to standard echocardiography methods during hospitalization including the day of discharge. IVC collapsibility index (IVC-CI = Maximum IVC diameter-Inspiratory IVC diameter/maximum diameter; <0.5 representing hypervolemia) was calculated. Primary study endpoint was 30-day readmission. Research activities were independent of clinical decision-making. RESULTS: Data for 106 patients was analyzed. Mean age was 66.7 ± 13.8 years, of which 53.8% were females, and a mean ejection fraction was 39 ± 18%. Initial scan of the IVC was obtained at an average time of 5.2 ± 8.04 hours from first diuretic dose. 81.2% of patients at admission had an IVC-CI <0.5. 63.2% patients had an IVC-CI <0.5 at discharge. There were no significant differences in age, length of stay, diuretic dose, or 30-day readmissions between patients with a discharge IVC-CI <0.5 vs ≥ 0.5. CONCLUSION: Hand-held ultrasound assessment of IVC-CI in ADHF patients, although a feasible concept, is unable to predict 30-day readmissions in our study. Further prospective studies are necessary.

Dialysis access as a source of infective endocarditis in dialysis patients.

The incidence of Infective Endocarditis (IE) is higher in dialysis patients compared to the general population. A major risk factor for IE in this group stems from bacterial invasion during repeated vascular access. Previous studies have shown increased risk of bacteremia in patients with indwelling dialysis catheters compared to permanent vascular access. However, association between the development of IE and the type of dialysis access is unclear. We aimed to examine the associated types of intravascular access and route of infection in dialysis patients who were admitted with infective endocarditis at our center. All patients admitted to Albert Einstein Medical Center in Philadelphia with a diagnosis of infective endocarditis who were on chronic hemodialysis were identified from the hospital database for the period of 1/1/07 to 12/31/18. Modified Duke criteria was used to confirm the diagnosis of infective endocarditis. A total of 96 cases were identified. Of those, 57 patients had an indwelling dialysis catheter while the other 39 had permanent dialysis access. In 82% of patients with dialysis catheters, their dialysis access site was identified as the primary source of infection compared to 30% in those with permanent dialysis access (p<0.001). The number of dialysis catheters placed in the preceding 6 months was strongly associated with endocarditis resulting from the dialysis access site (OR = 3.202, p=0.025). Dialysis catheters are more likely to serve as the source of infection in dialysis patients developing IE compared to permanent dialysis access. Increased awareness of risk of IE associated with dialysis catheters is warranted.

Aortic stenosis calcium scoring in a racially mixed sample.

Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.

A simple technique for bedside estimation of left atrial pressure.

BACKGROUND: Distinguishing cardiac from noncardiac causes of dyspnea is clinically important, and a reliable noninvasive measure of left atrial pressure (LAP) is needed. Subtracting the peak systolic gradient between left ventricle (LV) and left atrium (LA) from the central systolic blood pressure (BP) should provide this measure. Using a commercially available blood pressure system incorporating applanation tonometry and bedside echocardiography, we tested this hypothesis in a broad spectrum of patients. METHODS: A total of 75 stable patients, scheduled for right heart catheterization for any reason, were included. Central systolic pressure was measured by a Sphygmocor® tonometry system; peak LV-LA gradient was calculated as 4*(peak mitral regurgitation (MR) velocity)2 . Microbubble contrast was used as needed to augment the MR signal. LAP estimates using central BP were compared with wedge pressure as were LAP estimates using brachial BP. RESULTS: Left atrial pressure estimates using central BP showed a good correlation with wedge pressure (r2  = 0.774, P < .0001) while estimates using brachial systolic BP did not (r2  = 0.157, P = .0006). Using central BP, correlations between LAP and wedge were similar among groups with varying degrees of MR and normal vs reduced ejection fraction. CONCLUSIONS: The use of central systolic BP and peak LV-LA gradient by bedside echocardiography holds promise as a noninvasive measure of LAP. Our results are similar to those provided using current guidelines for echocardiographic estimation of LAP. Increased precision in the measurement of LV-LA gradient would improve the accuracy of this new technique.

Aortic root and valve proportions: an example of the golden ratio?

Calcific aortic stenosis is the most common lesion requiring valve replacement. Transcutaneous procedures (TAVR) are rapidly increasing yet detailed information on aortic valve and root anatomy are sparse.  This study examined gated cardiac CT scans to make observations regarding the size and proportions of the valve leaflets, sinuses of Valsalva, and sinotubular junction. One hundred and fifty gated cardiac CT scans were performed for a variety of clinical indications. Area of each cusp (short axis plane) was measured along with sinus height (from leaflet base to sinotubular junction), sinus width (from central coaptation point to outer sinus edge), annular perimeter, perimeter at mid-sinus level, and perimeter at the sinotubular junction. The right coronary cusp was largest, the left cusp smallest, and the non-coronary cusp intermediate in size. Each cusp was larger in men than women, even after indexing for body surface area.  By contrast, indexed sinus width and height did not differ between genders. No significant differences were noted between races. Annular perimeter did not vary by age while the mid-sinus perimeter and sinotubular junction perimeter increased with age (p=0.01, r2 =0.05 and p=0.002, r2 =0.07).  Interestingly, the ratio of sinus height (average): annular radius was 1.69±0.18, very close to the "golden ratio" of 1.62 found throughout the natural world.  This might be important for proper vortex formation in the sinuses.

Usefulness of left ventricular strain analysis in patients with takotsubo syndrome during acute phase.

BACKGROUND: Takotsubo syndrome (TTS) is peculiar clinical condition often resembling an acute coronary syndrome and mostly affecting postmenopausal women after a stressful trigger. TTS was initially thought to be a relatively benign condition. However, current data have shown it may be associated with considerable inpatient morbidity and carry a small, but important, mortality risk. METHODS: We hypothesized that left ventricular (LV) regional and global longitudinal strain (GLS) assessed with 2D speckle tracking echocardiography could identify early systolic functional impairment and predict in-hospital cardiovascular events. We conducted a retrospective descriptive study reviewing patients with the discharge diagnosis of TCM between 2003 and 2016 at our institution. RESULTS: One hundred patients with TSS met the Modified Mayo Clinic criteria. Using 2D speckle tracking echocardiography, two independent cardiologists assessed the LV GLS as well as the longitudinal strain (LS) of 7 individual segments [basal-septal (BS); mid-septal (MS), apical-septal (AS), apex, basal-lateral (BL), mid-lateral (ML), and apical-lateral (AL)]. The inter-observer variability was <5%. Mean age was 69.1 years, 87% were females, and 53% were African Americans. Mean initial LV EF was 32% ± 9.8%. In univariate analysis, patients with worse BL, ML, and GLS profiles (means: -5.7; -3.3, and -4, respectively) had higher in-hospital mortality (P < .05). Worse BL and ML profiles (means: -8.6 and -7.3, respectively) were associated with higher prevalence of MACE (major adverse cardiovascular outcomes) (P < .05). In a multivariate analysis, mid-lateral strain ≥ -7 and basolateral strain ≥ -10 were independent predictors of in-hospital mortality and MACE + in-hospital heart failure, respectively. CONCLUSIONS: Assessment of LV global and segmental longitudinal strain by speckle tracking has important prognostic value in the acute phase of TTS. Additional large-scale studies will be needed to confirm our findings.

Natural history of severe aortic stenosis: Diastolic wall strain as a novel prognostic marker.

BACKGROUND AND AIM: Diastolic wall strain (DWS) has been proposed as a simple noninvasive measure of left ventricular (LV) stiffness. This study investigated DWS as a possible predictor of mortality in severe aortic stenosis (AS). METHODS: 138 patients with severe AS (indexed aortic valve area [AVA]<0.6 cm2 /m2 ) and normal ejection fraction (>55%) were included. 52 patients (38%) had aortic valve interventions or poor image quality (n=5) and were excluded leaving 86 in the study group (84±8 years, 70% female, 69% African American). DWS was defined as (LVPWs-LVPWd)/LVPWs where LVPWs=left ventricular posterior wall thickness in systole and LVPWd=left ventricular wall thickness in diastole. RESULTS: Follow-up extended 2.0±1.9 years (median 1.6 years). Mean DWS for the group was 0.21±0.11 (normal=0.4±0.07). In patients who died, DWS was significantly lower than in survivors (0.18±0.09 vs 0.24±0.11, P=.02). By contrast, traditional measures of diastolic dysfunction did not predict death. Regression analysis showed DWS predicted death even after adjusting for age, sex, race, indexed AVA, symptoms (angina, shortness of breath, dizziness, syncope), and clinical factors (creatinine, smoking, diabetes, hypertension, hyperlipidemia) (HR 2.5 [95% CI 1.02-5.90], P<.05). The best cutoff value for DWS of 0.25 had a sensitivity of 42% and specificity of 83% for predicting death. CONCLUSIONS: DWS is an independent predictor of all-cause mortality in patients with severe AS, even after accounting for traditional clinical and echocardiographic parameters.

The Role of Medical Therapy in Moderate to Severe Degenerative Mitral Regurgitation.

Mitral regurgitation (MR) is a common valvular disorder that has important health and economic consequences. Standardized guidelines exist regarding when and in whom to perform mitral valve surgery, but little information is available regarding medical treatment of MR. Many patients with moderate or severe MR do not meet criteria for surgery or are deemed to be at high risk for surgical therapy. We reviewed the available published data on medical therapy in the treatment of patients with primary MR. b-blockers and renin-angiotensin-aldosterone system inhibitors had the strongest supporting evidence for providing beneficial effects. b-blockers appear to lessen MR, prevent deterioration of left ventricular function, and improve survival in asymptomatic patients with moderate to severe primary MR. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy reduces MR, especially in asymptomatic patients. However, in the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators can increase the severity of MR. To define the precise role of medical therapy, a larger randomized controlled trial is needed to confirm benefit and assess in which subsets of patients medical therapy is most useful. Medical therapy in some patients improves symptoms, lessens MR, and may delay the need for surgical intervention.

Antiplatelet therapy in Takotsubo cardiomyopathy: does it improve cardiovascular outcomes during index event?

Plasma catecholamines may play an important role in Takotsubo cardiomyopathy (TCM) pathophysiology. Patients with disproportionately high catecholamine responses to stressful events are prone to worse clinical outcomes. Catecholamines stimulate platelet activation and, therefore, may determine the clinical presentation and outcomes of TCM. We conducted a retrospective, descriptive study TCM patients admitted between 2003 and 2013 to Einstein Medical Center, Philadelphia, PA, USA and Danbury Hospital, Danbury, CT, USA. A total of 206 patients met Modified Mayo TCM criteria. Using a multiple logistic model, we tested whether aspirin, dual antiplatelet therapy (DAPT) aspirin + clopidogrel, beta blocker, statin, or ACE inhibitor use were independent predictors of major adverse cardiovascular events (MACE) during the index hospitalization. MACE was defined as in-hospital heart failure, in-hospital death, stroke or respiratory failure requiring mechanical ventilation. Incidence of in-hospital heart failure was 26.7 %, in-hospital death was 7.3 %, stroke was 7.3 % and MACE was 42.3 %. In a multiple logistic regression model (adjusted for gender, race, age, physical stressor, hypertension, diabetes, hyperlipidemia, smoking history, body mass index, initial left ventricular ejection fraction, single antiplatelet therapy, DAPT, beta blocker, statin, and ACE inhibitor) aspirin and DAPT at the time of hospitalization were independent predictors of a lower incidence of MACE during the index hospitalization (aspirin: OR 0.4, 95 % CI (0.16-0.9), P = 0.04; DAPT: OR 0.23; 95 % CI (0.1-0.55); P < 0.01. Physical stressor itself was also found to be an independent predictor of worse MACE: OR 5.1; 95 % CI (2.4-11.5); P < 0.01. In our study, aspirin and DAPT were independent predictors of a lower incidence of MACE during hospitalization for TCM. Prospective clinical trials are needed to confirm the findings of this study.

Distinctive Electrocardiographic Features in African Americans Diagnosed with Takotsubo Cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TC) can resemble acute anterior ST-elevation myocardial infarction. Most studies have examined TC in Asians and Caucasians (non-African Americans [AA]), while very few cases have been reported in AA. We aimed to assess the electrocardiographic features of TC in AA patients and compare them to non-AA TC patients. METHODS: We retrospectively compared electrocardiograms of 52 AA and 47 non-AA patients diagnosed with TC. All patients met the modified Mayo Clinic criteria for the diagnosis of TC. Information collected included PR interval, QRS duration and amplitude, QT interval in milliseconds (msec) adjusted for heart rate (QTc), ST-segment deviation at the J point in limb and precordial leads (≥1 mm), ST elevation (≥1 mm), and T-wave inversion (≥0.5 mm). RESULTS: T-wave inversion was more prevalent on presentation among AA patients (82% vs 48% in non-AA; P < 0.01), whereas ST depression was more common among non-AA (21% vs 7% in AA; P = 0.05). T-wave inversions in AA patients were frequent in both limb and precordial leads, whereas T-wave inversions in non-AA were limited to precordial leads. The average QTc upon presentation in AA was longer than non-AA (491 msec in AA vs 456 msec in non-AA; P < 0.01) as was the maximum average QTc during index hospitalization (527 msec in AA vs 497 msec in non-AA, P = 0.03). CONCLUSION: In patients presenting with TC, AA patients more frequently present with diffuse T-wave inversions and a more prolonged QTc, whereas non-AA patients more often present with ST depressions. AA patients also more frequently present with T-wave inversions diffusely, whereas non-AA patients present with T-wave inversions more limited to the precordial leads.

Daytime cardiac repolarization in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) has been implicated in complications of cardiovascular disease, including arrhythmias and sudden cardiac death (SCD). Prolonged QT interval is associated with arrhythmias and SCD in patients with cardiovascular disease and apparently healthy humans. Apneic episodes during sleep in OSA patients are associated with QT prolongation due to increased vagal activity, but it is not understood whether chronic QT prolongation persists during normoxic daytime wakefulness. METHODS: To determine whether daytime QT intervals in OSA patients are prolonged compared to control subjects, we recruited 97 (76 male, 21 female) newly diagnosed patients with OSA [apnea-hypopnea index (AHI) ≥5 events/h] and 168 (100 male, 68 female) healthy volunteers (AHI <5 events/h) and measured daytime resting QT and RR intervals from the electrocardiograms to determine QT prolongation corrected for heart rate (QTc). RESULTS: All subjects with OSA were older and heavier, with increased heart rate, significantly increased AHI and arousal index, and reduced oxygen saturation (SpO2) during sleep, and spent less time in sleep with >90 % SpO2 compared to respective controls. QTc in patients with OSA (410 ± 3.3 for male and 433 ± 5.6 for female) was significantly increased compared to respective control groups (399 ± 2.9 for male and 417 ± 2.9 for female), after adjustment for age and body mass index. CONCLUSIONS: Our data show that OSA in either men or women is associated with a significant increase in resting daytime QTc. The propensity for ventricular arrhythmias in patients with OSA may be a result of abnormalities in resting cardiac repolarization.

Tricuspid Annular Plane Systolic Excursion and Its Association with Mortality in Critically Ill Patients.

BACKGROUND: Transient left ventricular dysfunction can occur under conditions of extreme emotional or physiological stress. There is little data on right ventricular function in such situations. METHODS: One hundred twenty patients admitted to an ICU with a noncardiac illness were studied. Those with documented coronary disease, ejection fraction <40%, sepsis, or intracranial hemorrhage were excluded. Echocardiograms were performed within 24 hours of admission. Tricuspid annular plane systolic excursion (TAPSE) was measured to assess right ventricular systolic function. Plasma catecholamines (norepinephrine, epinephrine, dopamine) were measured on admission. Clinical and demographic data were collected, along with data on ICU length of stay (LOS), hospital LOS, and in-hospital and long-term mortality. TAPSE was tested for correlation with adverse outcomes and length of stay. RESULTS: Mean TAPSE for the group was 2.05 ± 0.66 cm. Based on area under the ROC curve analysis, TAPSE <2.4 cm was the best cutoff for predicting in-hospital and long-term mortality. There were 13 in-hospital deaths, 12 in the group with TAPSE <2.4 cm and one among those with TAPSE ≥2.4 cm. On multivariate analysis, TAPSE <2.4 cm was a significant predictor of in-hospital mortality (χ(2)  = 4.6, P = 0.03). When tested against hospital LOS, an inverse correlation was found (P = 0.04). No association was found between TAPSE and catecholamine levels. CONCLUSIONS: Right ventricular systolic function, as assessed by TAPSE, has important prognostic value in critically ill patients. Mean values were lower in patients who died in-hospital versus those who survived to discharge. In addition, patients with TAPSE <2.4 cm had a longer hospital length of stay.

Recurrent right ventricular takotsubo cardiomyopathy in a patient with recurrent aspiration.

Takotsubo cardiomyopathy is described as transient hypokinesis of the apical and mid-segments of the left ventricle with hypercontractile basal segments triggered by emotional or physical stress. Variants with basal hypokinesis and apical hyperkinesis have been described, as well as simultaneous involvement of the right ventricle (RV). Proposed mechanisms include myocardial "stunning" due to excessive catecholamine release. The echocardiographic presentation of Takotsubo cardiomyopathy may be related to differences in regional sympathetic innervation and catecholamine receptor density in the myocardium in the setting of high levels of circulating catecholamines. We describe the first case of isolated, recurrent RV Takotsubo cardiomyopathy reported in the literature.

The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). IN addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.

In vitro comparison of Doppler and catheter-measured pressure gradients in 3D models of mitral valve calcification.

Mitral annular calcification (MAC) involves calcium deposition in the fibrous annulus supporting the mitral valve (MV). When calcification extends onto the leaflets, valve opening can be restricted. The influence of MAC MV geometry on Doppler gradients is unknown. This study describes a novel methodology to rapid-prototype subject-specific MAC MVs. Replicated valves were used to assess the effects of distorted annular-leaflet geometry on Doppler-derived, transmitral gradients in comparison to direct pressure measurements and to determine if transmitral gradients vary according to measurement location. Three-dimensional echocardiography data sets were selected for two MAC MVs and one healthy MV. These MVs were segmented and rapid prototyped in their middiastolic configuration for in vitro testing. The effects of MV geometry, measurement modality, and measurement location on transmitral pressure gradient were assessed by Doppler and catheter at three locations along the MV's intercommissural axis. When comparing dimensions of the rapid-prototyped valves to the subject echocardiography data sets, mean relative errors ranged from 6.2% to 35%. For the evaluated MVs, Doppler pressure gradients exhibited good agreement with catheter-measured gradients at a variety of flow rates, though with slight systematic overestimation in the recreated MAC valves. For all of the tested MVs, measuring the transmitral pressure gradient at differing valve orifice positions had minimal impact on observed gradients. Upon the testing of additional normal and calcific MVs, these data may contribute to an improved clinical understanding of MAC-related mitral stenosis. Moreover, they provide the ability to statistically evaluate between measurement locations, flow rates, and valve geometries for Doppler-derived pressure gradients. Determining these end points will contribute to greater clinical understanding for the diagnosis MAC patients and understanding the use and application of Doppler echocardiography to estimate transmitral pressure gradients.