Using Artificial Intelligence to Semi-Quantitate Coronary Calcium as an 'Incidentaloma' on Non-Gated, Non-Contrast CT Scans, A Single-Center Descriptive Study in West Michigan.

INTRODUCTION: Non-gated, non-contrast computed tomography (CT) scans are commonly ordered for a variety of non-cardiac indications, but do not routinely comment on the presence of coronary artery calcium (CAC)/atherosclerotic cardiovascular disease (ASCVD) which is known to correlate with increased cardiovascular risk. Artificial intelligence (AI) algorithms can help detect and quantify CAC/ASCVD which can lead to early treatment and improved outcomes. METHODS: Using an FDA-approved algorithm (NANOX AI) to measure coronary artery calcium (CAC) on non-gated, non-contrast CT chest, 536 serial scans were evaluated in this single-center retrospective study. Scans were categorized by Agatston scores as normal-mild (<100), moderate (100-399), or severe (≥400). AI results were validated by cardiologist's overread. Patient charts were retrospectively analyzed for clinical characteristics. RESULTS: Of the 527 patients included in this analysis, a total of 258 (48.96%) had moderate-severe disease; of these, 164 patients (63.57%, p< 0.001) had no previous diagnosis of CAD. Of those with moderate-severe disease 135 of 258 (52.33% p=0.006) were not on aspirin and 96 (37.21% p=0.093) were not on statin therapy. Cardiologist interpretation demonstrated 88.76% agreement with AI classification. DISCUSSION/CONCLUSION: Machine learning utilized in CT scans obtained for non-cardiac indications can detect and semi-quantitate CAC accurately. Artificial intelligence algorithms can accurately be applied to non-gated, non-contrast CT scans to identify CAC/ASCVD allowing for early medical intervention and improved clinical outcomes.

Impact of aortic valve replacement in symptomatic low-risk patients with less than severe aortic stenosis.

OBJECTIVE: To evaluate whether transcatheter or surgical aortic valve replacement (TAVR or SAVR) affects clinical and haemodynamic outcomes in symptomatic patients with moderately-severe aortic stenosis (AS). METHODS: Echocardiographic evidence of severe AS for enrolment in the Evolut Low Risk trial was based on site-reported measurements. For this post hoc analysis, core laboratory measurements identified patients with symptomatic moderately-severe AS (1.0

Preservation of Cardiopulmonary Function in Patients Treated with Ultrasound-Accelerated Thrombolysis in the Setting of Submassive Pulmonary Embolism.

PURPOSE: To evaluate the clinical effectiveness of ultrasound-assisted thrombolysis (USAT) in resolution of right ventricular dysfunction (RVD), preservation of cardiopulmonary function, and quality of life (QoL) in patients with acute submassive pulmonary embolism (PE). MATERIALS AND METHODS: A single-center prospective study of patients presenting with acute PE and signs of RVD, as determined by right ventricle-to-left ventricle diameter ratio (RV:LV) > 0.9 on computed tomographic angiography of the thorax, was performed. Patients underwent USAT with recombinant tissue plasminogen activator. Primary endpoints measured were RV:LV by echocardiogram at baseline presentation and at 72 hours and 90 days after treatment. Secondary endpoints were QoL scores assessed by SF-36 Health Surveys at baseline and at 90 days, cardiopulmonary exercise test (CPET) parameters at 90 days, and procedural outcomes, including response of pulmonary artery pressure (PAP) and procedural complications. RESULTS: Twenty-five patients were treated between June 17, 2013, and September 15, 2014, with mean reduction of RV:LV by echocardiogram from 1.38 ± 0.28 at presentation to 0.92 ± 0.14 (P < .0001) at 72 hours and 0.84 ± 0.25 (P < .0001) at 90 days. SF-36 Health Survey scores demonstrated no long-term self-perceived adverse physical or mental effects as a result of PE. CPET parameters, including VO2max, weight-adjusted VO2, VE/VCO2, and VD/VT demonstrated no pulmonary vascular impairment at 90 days. PAP significantly improved after USAT, with mean initial systolic pressure of 50.46 ± 13.98 mmHg reduced to 39.64 ± 8.66 mmHg (P = .0001). There were no deaths, recurrent venous thromboembolism, hemodynamic decompensation, or hemorrhage. CONCLUSIONS: USAT resulted in significant reduction of RV:LV at 72 hours, which was preserved at 90 days. QoL and objective measures of cardiopulmonary function are preserved at 90 days in this population. Further studies with long-term follow-up are needed to determine the potential value of USAT for the prevention of post-PE syndrome in patients with submassive PE.

Right ventricular free wall stress after tricuspid valve annuloplasty in acute ovine right heart failure.

BACKGROUND: Tricuspid annuloplasty rings may have a direct impact on right ventricular shape and free wall stress, potentially affecting chamber remodeling and recurrent regurgitation. In an acute model of ovine right heart failure, we investigated right ventricular free wall stress after annuloplasty with different prostheses. METHODS: Thirty-xix sheep underwent implantation of sonomicrometry crystals on the tricuspid annulus and right ventricle. Each group consisted of 9 animals that received a flexible (28 ± 1 mm), rigid (29 ± 1 mm), or flexible-rigid hybrid (28 ± 1 mm) ring. Nine control animals had no ring implanted. Hemodynamic, sonomicrometry, and echocardiographic data were collected before (baseline-control group) and during acute right heart failure (control and ring groups). Free wall stress was calculated using the modified Laplace formula for thick shells. Ventricular geometry was determined from 3-dimensional crystal coordinates. RESULTS: Acute right heart failure reduced right ventricular deformation and fractional volume change while increasing pressure, tricuspid regurgitation grade, cross-sectional area, and free wall stress in control animals versus baseline. All rings significantly decreased right ventricular free wall stress versus control except rigid ring at end-systole. There was no significant difference in free wall stress or tricuspid regurgitation between any ring group during acute heart failure and baseline-control group. No significant difference in free wall stress was observed between any of the ring groups. CONCLUSIONS: Acute right heart failure significantly increased right ventricular free wall stress, which was normalized with equal efficacy by all studied prostheses. Chronic studies are needed to evaluate long-term effects of annuloplasty rings on right ventricle free wall stress and remodeling.

Tricuspid Annular Geometry and Strain After Suture Annuloplasty in Acute Ovine Right Heart Failure.

BACKGROUND: Tricuspid valve repair using suture annuloplasty is thought to be more physiologic, but the effect of annular reduction on annular geometry and motion is unknown. We set out to investigate the effect of DeVega suture annuloplasty (DV) on tricuspid annular geometry and dynamics during acute right heart failure (RHF). METHODS: Ten adult sheep underwent implantation of sonomicrometry crystals around the tricuspid annulus and on the right ventricle; pressure transducers were placed in right ventricle, left ventricle, and right atrium. RHF was induced by a combination of 500 mL volume infusion, posterior descending artery occlusion, and pulmonary artery constriction. Hemodynamic, echocardiographic, and sonomicrometry data were acquired at baseline, with RHF, and after two progressive (8 to 10 mm) DV suture cinches (DV-1, DV-2) during RHF. Annular size, geometry, and dynamics were determined from crystal coordinates. RESULTS: Combination of volume infusion, ischemia, and pulmonary hypertension resulted in acute RHF and significant functional tricuspid regurgitation grade (0.5 ± 0.5 versus 2.7 ± 0.8, p < 0.001). Annular area increased with RHF from 700 ± 98 mm2 to 801 ± 128 mm2 (p < 0.001). DV-1 and DV-2 reduced annular area to 342 ± 88 mm2 and 180 ± 57 mm2 while reducing regurgitation grade to 1.2 ± 0.4 and 0.4 ± 0.5, respectively (all p < 0.001 versus RHF). Tricuspid annular area contraction was 12% ± 7%, 10% ± 6%, and 12% ± 6% for RHF, DV-1, and DV-2, respectively (p = 0.25) and annular height was 4.9 ± 2.0 mm, 5.6 ± 1.4 mm, and 5.5 ± 1.7 mm (p = 0.43). Mean transvalvular gradient was 1.3 ± 0.7 mm Hg and 2.0 ± 1.0 mm Hg with DV-1 and DV-2, respectively. CONCLUSIONS: During acute ovine RHF, DeVega annuloplasty successfully treated tricuspid regurgitation and preserved normal tricuspid annular dynamics and geometry. These data may lead to more physiologic tricuspid reparative techniques.

Tricuspid valvular dynamics and 3-dimensional geometry in awake and anesthetized sheep.

OBJECTIVES: Clinical and experimental tricuspid valve physiology data are derived predominantly from anesthetized subjects, but normal tricuspid valve geometry and dynamics may be altered by general anesthesia and mechanical ventilation. We set out to investigate 3-dimensional geometry and dynamics of the tricuspid valve complex in awake and anesthetized sheep. METHODS: While on cardiopulmonary bypass and with the heart beating, 6 adult sheep (50 ± 8 kg) underwent implantation of 6 sonomicrometry crystals around the tricuspid annulus. One crystal was implanted on the anterior, posterior, and septal papillary muscle tips, 4 on the right ventricular free wall and 1 on its apex. Pressure transducers were placed in both ventricles. Sonomicrometry and pressure transducer cables were externalized to subcutaneous buttons. After 7 days of recovery, hemodynamic and sonomicrometry data were recorded with animals awake and anesthetized. RESULTS: Hemodynamic parameters did not differ between groups. Tricuspid annular area contraction decreased with anesthesia (16.4% ± 4.2% vs 11.2% ± 3.2%, P = .047) as did tricuspid annular perimeter contraction (8.1% ± 2.2% vs 5.4% ± 1.7%, P = .050), predominantly due to reduced contraction of the septal annulus (10.5% ± 2.9% vs 7.5% ± 3.5%, P = .019). Tricuspid annular height did not differ between groups. Minimal distance from anterior, posterior, and septal papillary muscle tips to the annular plane did not change with anesthesia. Regional right ventricle free wall contraction was depressed under anesthesia in anterior (16.3% ± 3.1% vs 12.3% ± 2.2%, P = .027) and lateral (14.9% ± 1.3% vs 11.5% ± 2.8%, P = .016) segments, whereas the posterior remained unchanged. CONCLUSIONS: General anesthesia did not alter tricuspid annular or subvalvular 3-dimensional geometry but reduced right ventricular contraction and tricuspid annular dynamics.

Large animal model of acute right ventricular failure with functional tricuspid regurgitation.

BACKGROUND: Functional tricuspid regurgitation (FTR) commonly arises secondary to conditions affecting the left heart and is associated with right ventricular dysfunction and tricuspid annular dilatation. We set out to establish an animal model of acute RV failure (RVF) with FTR resembling the clinical features. METHODS: Ten adult sheep had pressure sensors placed in the LV, RV, and right atrium while sonomicrometry crystals were implanted around tricuspid annulus and on the RV. Animals were studied open-chest to assess for RV function and FTR after: (1) volume infusion, (2) pulmonary artery constriction, (3) 5 min posterior descending artery occlusion, and (4) combination of all interventions. Hemodynamic, echocardiographic, and sonomicrometry data were collected at baseline and after every intervention. RV dimensions, RV strain, and annular area, perimeter, and size were calculated from crystal coordinates. The model was validated in six additional sheep studied only before and after combined interventions. RESULTS: Neither volume infusion, pulmonary hypertension, nor ischemia were associated with RVF or clinically significant TR when applied separately but combined resulted in RVF and greater than moderate FTR. In the validation group, maximal RV volume increased (62 ±â€¯14 vs 70 ±â€¯16 ml, p = 0.006), contractility decreased (20 ±â€¯6 vs 12 ±â€¯2%, p = 0.02), and strain increased. FTR increased from 0.4 ±â€¯0.5 to 2.5 ±â€¯0.8 (p < 0.001) and annular area from 652 ±â€¯87 mm2 to 739 ±â€¯87 mm2 (p = 0.005). CONCLUSIONS: The developed ovine model of acute RVF was associated with significant annular and RV enlargement and FTR. This novel and clinically pertinent research platform offers insight into the acute RVF pathophysiology and can be utilized to evaluate treatment interventions.

Feasibility of transthoracic echocardiographic imaging in non-sedated ovine subjects using a commercial restraint device.

Transthoracic echocardiography (TTE) is a valuable non-invasive imaging research technique. In ovine models of cardiac disease, restraint for TTE often involves sedation even with currently available restraint equipment; our goal was to determine the feasibility of using a commercial restraint device, commonly known as the sheep chair, in minimizing animal stress and the need for sedation while achieving a complete TTE examination. A total of 10 healthy adult Dorset sheep were restrained in a sheep chair for TTE and observed for signs of stress. No animals displayed overt evidence of stress and none required sedation. While individual anatomic variation existed, image quality was sufficient to determine cardiac function. These observations suggest that a sheep chair is a useful aid in minimizing the need for sedation to acquire a full TTE study in ovine subjects.

Multimodality Intracoronary Imaging With Near-Infrared Spectroscopy and Intravascular Ultrasound in Asymptomatic Individuals With High Calcium Scores.

BACKGROUND: This study sought to determine the frequency of large lipid-rich plaques (LRP) in the coronary arteries of individuals with high coronary artery calcium scores (CACS) and to determine whether the CACS correlates with coronary lipid burden. METHODS AND RESULTS: Combined near-infrared spectroscopy and intravascular ultrasound was performed in 57 vessels in 20 asymptomatic individuals (90% on statins) with no prior history of coronary artery disease who had a screening CACS ≥300 Agatston units. Among 268 10-mm coronary segments, near-infrared spectroscopy images were analyzed for LRP, defined as a bright yellow block on the near-infrared spectroscopy block chemogram. Lipid burden was assessed as the lipid core burden index (LCBI), and large LRP were defined as a maximum LCBI in 4 mm ≥400. Vessel plaque volume was measured by quantitative intravascular ultrasound. Vessel-level CACS significantly correlated with plaque volume by intravascular ultrasound (r=0.69; P<0.0001) but not with LCBI by near-infrared spectroscopy (r=0.24; P=0.07). Despite a high CACS, no LRP was detected in 8 (40.0%) subjects. Large LRP having a maximum LCBI in 4 mm ≥400 were infrequent, found in only 5 (25.0%) of 20 subjects and in only 5 (1.9%) of 268 10-mm coronary segments analyzed. CONCLUSIONS: Among individuals with a CACS ≥300 Agatston units mostly on statins, CACS correlated with total plaque volume but not LCBI. This observation may have implications on coronary risk among individuals with a high CACS considering that it is coronary LRP, rather than calcification, that underlies the majority of acute coronary events.

Large animal model of functional tricuspid regurgitation in pacing induced end-stage heart failure.

OBJECTIVES: Functional tricuspid regurgitation (FTR) is common in patients with advanced heart failure and frequently complicates left ventricular assist device implantation yet remains poorly understood. We set out to establish large animal model of FTR that could serve as a research platform to investigate the pathogenesis of FTR associated with end-stage heart failure. METHODS: : Through right thoracotomy, ten adult sheep underwent implantation of pacemaker with epicardial LV lead, five sonomicrometry crystals on the right ventricle, and left and right ventricular telemetry pressure sensors during a beating heart off-pump procedure. After 5 ± 1 days of recovery, baseline haemodynamic, echocardiographic and sonomicrometry data were collected. Animals were paced thereafter at a rate of 220-240 beats/min until the development of heart failure and concomitant tricuspid regurgitation. RESULTS: : Three animals died during early recovery period and one during the pacing phase. Six surviving animals were paced for a mean of 14 ± 5 days. Cardiac function was significantly depressed compared to baseline, with LV ejection fraction falling from 69 ± 2% to 22 ± 4% ( P < 0.001) and RV fractional area change from 52 ± 11% to 25 ± 9% ( P = 0.005). All animals developed significant enlargement of tricuspid annulus (from 29.5 ± 1.6 to 36.5 ± 4.5 mm; P = 0.01) and right ventricle (from 21.9 ± 0.2 to 30.3 ± 0.6 mm; P = 0.03). Sonomicrometry derived contractility of RV free wall was depressed and at least moderate tricuspid insufficiency developed in all animals. CONCLUSIONS: : Biventricular dysfunction, tricuspid annular dilatation and significant FTR were observed in our model of ovine tachycardia induced cardiomyopathy. This animal model reflects the clinical situation of end-stage heart failure patients presenting for mechanical support.

The effect of acute mechanical left ventricular unloading on ovine tricuspid annular size and geometry.

OBJECTIVES: Left ventricular assist device (LVAD) implantation may alter right ventricular shape and function and lead to tricuspid regurgitation. This in turn has been reported to be a determinant of right ventricular (RV) failure after LVAD implantation, but the effect of mechanical left ventricular (LV) unloading on the tricuspid annulus is unknown. The aim of the study was to provide insight into the effect of LVAD support on tricuspid annular geometry and dynamics that may help to optimize LV unloading with the least deleterious effect on the right-sided geometry. METHODS: In seven open-chest anaesthetized sheep, nine sonomicrometry crystals were implanted on the right ventricle. Additional nine crystals were implanted around the tricuspid annulus, with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Left ventricular unloading was achieved by connecting a cannula in the left atrium and the aorta to a continuous-flow pump. The pump was used for 15 min at a full flow of 3.8 ± 0.3 l/min. Epicardial echocardiography was used to assess the degree of tricuspid insufficiency. Haemodynamic, echocardiographic and sonomicrometry data were collected before and during full unloading. Tricuspid annular area, and the regional and total perimeter were calculated from crystal coordinates, while 3D annular geometry was expressed as the orthogonal distance of each annular crystal to the least squares plane of all annular crystals. RESULTS: There was no significant tricuspid regurgitation observed either before or during LV unloading. Right ventricular free wall to septum diameter increased significantly at end-diastole during unloading from 23.6 ± 5.8 to 26.3 ± 6.5 mm (P = 0.009), but the right ventricular volume, tricuspid annular area and total perimeter did not change from baseline. However, the septal part of the annulus significantly decreased its maximal length (38.6 ± 8.1 to 37.9 ± 8.2 mm, P = 0.03). Annular contraction was not altered. The tricuspid annulus had a complex 3D saddle-shaped geometry that was unaffected during experimental conditions. CONCLUSIONS: In healthy sheep hearts, left ventricular unloading increased septal-free wall RV diameter and reduced the length of the septal annulus, without altering the motion or geometry of the tricuspid annulus. Acute left ventricular unloading alone in healthy sheep was not sufficient to significantly perturb tricuspid annular dynamics and result in tricuspid insufficiency.

The effect of pulmonary hypertension on ovine tricuspid annular dynamics.

OBJECTIVES: Pulmonary hypertension (PHT) is associated with tricuspid annular dilatation, but the effect of acute increase of pulmonary pressure on three-dimensional (3D) tricuspid annular dynamics and shape is unknown. Better understanding of tricuspid annular dynamics may lead to improved and more durable surgical reparative techniques. METHODS: In nine open-chest anaesthetized sheep nine sonomicrometry crystals were implanted on the right ventricle while on cardiopulmonary bypass. Additional nine crystals were implanted around the tricuspid annulus (TA) with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Two additional equidistant crystals were implanted between each commissure, creating three segments for every region. Pressure transducers were placed in the left ventricular (LV), right ventricular (RV) and right atrium. PHT was induced by acute pulmonary artery constriction with a pneumatic occluder. Sonomicrometry and echocardiographic data were collected before and after induction of PHT. TA area, regional and total perimeter, and 3D annular geometry were calculated from 3D crystal coordinates. Regional annular contraction was defined as the percentage difference between maximal and minimal region length during the cardiac cycle. RESULTS: PHT increased RV pressure from 31 ± 9 mmHg to 46 ± 13 mmHg (P = 0.001) and decreased left ventricular (LV) pressure from 111 ± 24 mmHg to 78 ± 36 mmHg (P = 0.018). There was no significant tricuspid regurgitation observed with PHT. During PHT, the TA area increased by 12 ± 13% from 641 ± 139 mm(2) to 721 ± 177 mm(2) (P = 0.037). The total perimeter increased from 103 ± 11 mm to 109 ± 13 mm (P = 0.02). All annular regions dilated significantly with PHT with 8 ± 10, 5 ± 5 and 5 ± 5% increase in anterior, posterior and septal annular length, respectively (P < 0.05). PHT reduced regional annular contraction in the anterior region only (17 ± 7 vs 14 ± 8%; P = 0.02). The TA had a complex 3D saddle geometry and the shape of the annulus was altered during PHT only in the antero-posterior region. CONCLUSIONS: The changes in tricuspid annular conformation, contractility and its 3D geometry observed during acute ovine PHT may help in the design of new pathology-specific tricuspid annular rings.

Genetic Factors Influencing B-type Natriuretic Peptide-Mediated Production of Cyclic Guanosine Monophosphate and Blood Pressure Effects in Heart Failure Patients.

Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). We explored genetic determinants of pharmacodynamic effects of B-type NP (BNP) and changes in plasma cyclic guanosine monophosphate (cGMP) and blood pressure (BP). HF patients (n = 135) received recombinant human BNP (nesiritide) at standard doses, and plasma cGMP levels were measured at baseline and during infusion. We tested the association of 119 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NPR1, NPR2, NPR3, and membrane metallo-endopeptidase (MME)) with the change in cGMP and BP. Gene-based testing for association of genetic variation with endpoints was significant only for MME. Upon individual SNP testing, two loci in MME were associated with ΔcGMP; another (rs16824656) showed association with BP change. In summary, the pharmacodynamic effects of BNP vary substantially in HF patients and are associated with genetic variation in MME. MME genetic variation may be an important determinant of NP-mediated effects in humans.

Genetic and nongenetic factors influencing pharmacokinetics of B-type natriuretic peptide.

BACKGROUND: Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). However, there is wide individual variability in NP system activity, which could be partly genetic in origin. We explored genetic and nongenetic contributions to B-type natriuretic peptide (BNP) inactivation. METHODS: Chronic HF patients (n = 95) received recombinant human BNP (nesiritide) at standard doses, and BNP levels were measured at baseline, after 2 hours of infusion, and 30 minutes after discontinuation. Genomic DNA was genotyped for 91 single-nucleotide polymorphisms (SNP) in 2 candidate genes. We tested the association of patient characteristics and genotype with 5 pharmacokinetics (PK) parameters: elimination rate constant, ΔBNP, BNP clearance, adjusted BNP clearance, and half-life. Linear regression with pleiotropic analysis was used to test genotype associations with PK. RESULTS: Participants' mean age was 63 years, 44% were female, and 46% were African American. PK parameters varied widely, some >10-fold. HF type (preserved vs reduced) was associated with PK (P < .01), whereas renal function, demographics, and body mass index and were not. Two SNPs in MME (rs989692, rs6798179) and 2 in NPR3 (rs6880564, rs2062708) also had associations with PK (P < .05). CONCLUSIONS: The pharmacokinetics of BNP varies greatly in HF patients, differs by HF type, and possibly by MME or NPR3 genotype. Additional study is warranted.