Introducing echocardiography to medical students: A novel echocardiography E-Learning experience.

BACKGROUND: Echocardiography is fundamental in the understanding of cardiology; however, echocardiography is not routinely taught in medical schools. The aim of this study is to assess whether teaching echocardiography to preclinical medical students using an e-learning software (ELS) is practical and appropriate. METHODS: From 2017 to 2019, 1084 second-year medical students at Indiana University School of Medicine were introduced to echocardiography by using the ELS. In 2017 and 2018 students had a postcourse survey to assess echocardiography appropriateness and cardiology learning. Students in 2018 and 2019 were assessed for any association between the use of the ELS and learning cardiology by comparing examination scores. RESULTS: In 2017-2018, 127 students responded to the survey (18% response rate). In 2017, 79% of responders and in 2018, 89% reported that introducing echocardiography to medical students is appropriate. In 2017, 78% and in 2018, 87% reported that it improved the understanding of cardiology. Student ELS usage was high for 2017-2018 (93% and 70%) but dropped in 2019 (30%). In 2018 and 2019, students who used ELS did statistically significantly better on the examination (total scores 84% vs. 82% (P = .008) in 2018; 84% vs. 81% (P = .002) in 2019). CONCLUSIONS: Many 2nd year medical students felt learning echocardiography with ELS was appropriate and enhanced their learning cardiology. Using echocardiography to help learn cardiology appears to be supported with an association of ELS usage and improved examination scores. Our study suggests that echocardiography learning can and probably should begin in medical school.

Safety and feasibility of dopamine-atropine stress echocardiography.

BACKGROUND: Dobutamine-atropine stress echocardiography (DSE) has lower sensitivity in patients with advanced liver disease (ALD) due to vasodilation. HYPOTHESIS: Dopamine-atropine stress echocardiography (DopSE) may be an alternative to DSE in ALD patients by improving the blood pressure response to stress. METHODS: The safety and tolerability of DSE and DopSE were compared in 10 volunteers. The safety, adverse effects, and efficacy of DopSE were then assessed in 105 patients, 98 of whom had ALD. Dopamine was infused in stepwise fashion from 5 µg/kg/min to a peak dose of 40 µg/kg/min. Atropine was given before and in early stages of dopamine infusion up to cumulative dose of 1.5 mg. The hemodynamic responses of 98 ALD patients were compared with 102 patients with ALD who underwent standard DSE. RESULTS: In normal volunteers, systolic BP increased more with DopSE compared to DSE (61 ± 19 mm Hg vs 39 ± 15 mm Hg, P = .008). In 105 patients who underwent DopSE, none had adverse effects that required early stress termination. In the groups with ALD, the systolic BP increase (38 ± 28 mm Hg vs 12 ± 27 mm Hg, P < .001) and peak rate pressure product (RPP) (22 861 ± 5289 vs 17 211 ± 3848, P = <.001) were both higher in those undergoing DopSE versus DSE. The sensitivity and specificity of DopSE were 45% and 88%, respectively for coronary disease (≥70% stenosis) in 37 patients who had angiography. CONCLUSIONS: Dopamine-atropine stress echocardiography appears to be a safe stress modality and provides greater increases in RPP in patients with ALD compared to DSE.

Prevalence, etiology, and clinical implications of reduced longitudinal systolic strain in renal transplant candidates.

AIMS: Reduced global longitudinal systolic strain (GLS) is a common finding in end-stage renal disease (ESRD) patients with normal ejection fraction (EF), and GLS is a stronger predictor of mortality than EF. We sought to determine what factors may be responsible for the decreased strain in this population. METHODS AND RESULTS: The study group was comprised of 139 renal transplant candidates with a normal EF who had echocardiography with assessment of GLS and basal longitudinal systolic strain (BLS). A GLS of less than -18 and a BLS less than -17 were defined as abnormal. Logistic regression was used to determine variables associated with abnormal GLS and BLS. Of the 139 patients, 49% had abnormal GLS and 70% had abnormal BLS. The univariate predictors of abnormal GLS (P<.05) were low-normal EF, increased interventricular septal thickness (IVS), diabetes, and dihydropyridine calcium channel blocker use. The univariate predictors of abnormal BLS (P<.05) were elevated systolic blood pressure, elevated diastolic blood pressure, elevated heart rate, decreased EF, increased IVS, increased left ventricular posterior wall thickness (LVPW), increased left ventricular mass index, regular dialysis, and clonidine use. On multivariate analysis, low-normal EF (P<.001), increased IVS (P=.024), and diabetes (P=.042) were independent predictors of abnormal GLS, while increased DBP (P=.018), increased LVPW (P=.001), and regular dialysis (P=.006) were independent predictors of abnormal BLS. CONCLUSIONS: Clinical variables and co-findings beyond EF are associated with abnormal strain measurements and may partially explain the large incidence of abnormal strain in renal transplant candidates.

Frequency, time course, and possible causes of right ventricular systolic dysfunction after cardiac transplantation: a single center experience.

BACKGROUND: The frequency and causes of right ventricular (RV) systolic dysfunction early after cardiac transplantation are not well defined. METHODS: We investigated the prevalence and causes of RV dysfunction in 27 heart transplant recipients, as measured by lateral tricuspid annular plane excursion (TAPSE) and fractional area change (FAC) at a mean of 15 ± 11 days after transplant. Tissue Doppler imaging was used to assess systolic time velocity integral (TVI) of the RV basal free wall. A subset of 22 patients had follow-up TAPSE measurement at 406 ± 121 days. RESULTS: RV systolic dysfunction, defined as TAPSE > 2 standard deviation (SD) below values in a control group, was present in 100% (27/27) of patients (P < 0.05). FAC was also significantly lower in patients compared with controls (P < 0.0001). TVI confirmed the presence of RV dysfunction in all 16 patients with both TAPSE and TVI (P < 0.05). Ischemic time (P = 0.017) and posttransplant tricuspid regurgitation (P = 0.024) were independent predictors of early RV dysfunction (r = 0.753). On follow-up, RV function improved in 15 of 22 patients but all patients remained with TAPSE > 2 SD below controls. CONCLUSION: This study showed that 100% of patients had reduced RV function early after transplant. Two thirds of patients had partial recovery of RV function during the first year. In all patients, however, RV function remained significantly lower than in controls.

Assessment of Postsystolic Shortening and Global Longitudinal Strain Improves the Sensitivity of Dobutamine Stress Echocardiography in End-Stage Liver Disease.

BACKGROUND: Dobutamine stress echocardiography (DSE) remains a widely used method for detection of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) despite low sensitivity. Speckle-tracking assessment of strain may enhance the sensitivity of DSE in the general population, but the value of strain analysis in ESLD is unknown. METHODS: Dobutamine stress echocardiography with two-dimensional speckle-tracking and quantitative coronary angiography were performed in 146 patients with ESLD. Thirty-six patients (25%) had CAD (≥50% diameter stenosis of a major vessel). Global longitudinal strain at rest (GLSr) and at peak stress (GLSp) and an index of postsystolic (PSSi) shortening ([maximal extent of shortening - extent of shortening in systole]/[extent of shortening in systole]) were determined. A PSSi of ≥ 0.25 was considered evidence for CAD. Receiver operating characteristic analysis was used to determine the optimal thresholds of GLSr and GLSp for CAD and to assess the diagnostic performance of visual assessment of wall motion (WMA) and strain parameters. The sensitivity and specificity of WMA, GLSr, GLSp, and PSSi were compared. RESULTS: Thirty-six patients (25%) had significant CAD. The areas under the curve for WMA, GLSr, GLSp, and PSSi were 0.60, 0.72, 0.68, and 0.78, respectively. Visual assessment of wall motion had a sensitivity of 28%. The sensitivity of each of the strain parameters, GLSr (53%, P = .016), GLSp (69%, P = .004), and PSSi (78%, P < .001), exceeded the sensitivity for WMA. Visual assessment of wall motion specificity was 92%, which exceeded the specificity for each of the strain parameters (GLSr = 82%, P = .037; GLSp = 63%, P < .001; and PSSi =78%, P = .009). Of the strain parameters, PSSi had the best balance between sensitivity and specificity (both 78%). CONCLUSION: Assessment of GLS and PSSi with DSE yields better sensitivity than WMA in ELSD patients. Index of postsystolic shortening had the best diagnostic performance of all parameters in this population with a low prevalence of CAD.

A practical approach to using strain echocardiography to evaluate the left ventricle.

Left ventricular (LV) evaluation is the most important use of echocardiography. Speckle tracking strain echocardiography (SE) provides a quantitative regional and global LV assessment, is an independent supplement to wall motion analysis and has been validated over the past 10 years. Despite these facts, SE is not being used routinely, especially in the United States. SE can generate longitudinal, radial, and circumferential strain measurements and LV twist. Although intriguing and potentially useful, these measurements also are confusing, complicated, time consuming, and frequently displayed as difficult-to-interpret wave forms. A pragmatic approach to SE simplifies the suggested method for strain calculation to reduce the time required and enhance reproducibility. With this modification the strain calculations take only 2-4 min. The yield is >80% in all patients. Reproducibility is at least as good as ejection fraction. Longitudinal strain is the most sensitive and reproducible of the various strain measurements, so it is the only strain we record. For simplicity, systolic strain is displayed as a positive number. Lastly, we primarily use a bullseye presentation for peak systolic strain. Many clinical examples are illustrated. However, as with all tests, SE is not perfect; there are limitations and potential false positives, but a practical approach to SE eventually should help make it a part of all echocardiographic examinations.

23rd Annual Feigenbaum Lecture: History of Echocardiography: A Personal Perspective.

Ultrasound was first used to examine the cardiovascular system about 70 years ago. The evolution of echocardiography as a family of diagnostic methods has been marked by ongoing development of novel technologies and clinical applications. The history is interesting and may be of particular interest to those practitioners who use echocardiography to enhance the care of their patients but who do not remember the "early days" of this field. In this article, based on the 23rd Feigenbaum Lecture, the authors discuss the history of echocardiography from the personal perspective of one of the clinicians, who has been a leader in this field for more than 60 years.

Effect of improvement in left ventricular ejection fraction on long-term survival in revascularized patients with ischaemic left ventricular systolic dysfunction.

AIMS: The importance of improvement in the ejection fraction to the prognosis of revascularized patients with ischaemic left ventricular (LV) dysfunction is uncertain. METHODS AND RESULTS: Eighty-seven patients with ischaemic LV dysfunction (mean ejection fraction 29 ± 8% by biplane Simpson's) had dobutamine echocardiography before revascularization (coronary bypass graft surgery-81, percutaneous intervention-6). Follow-up echocardiograms were performed a mean of 4.8 ± 6.2 months after revascularization. An 8% increase in the ejection fraction was considered significant (two times the inter-observer difference of 3.7%). Patients were followed for cardiac death. During a mean follow-up of 5.2 ± 3.9 years, there were 20 (23%) cardiac deaths. Class 3/4 heart failure, increasing low-dose wall motion score, increasing % non-viable myocardium, and digoxin use in follow-up were univariate predictors of death. Beta-blocker use, ejection fraction improvement, angina, aspirin use, and increasing fractional shortening were univariate predictors of survival. Ejection fraction improvement [P= 0.02, hazard ratio (HR) = 0.26], digoxin use in follow-up (P= 0.006, HR = 5.85), and low-dose wall motion score (P= 0.017, HR = 4.78) were independent predictors of outcome. In step-wise analysis, low-dose wall motion score added incremental prognostic value to ejection fraction improvement (P= 0.003), and digoxin use in follow-up (P= 0.003) added incremental value to a low-dose score and ejection fraction improvement. CONCLUSION: Ejection fraction improvement is an independent predictor of long-term outcome in revascularized patients but viability (low-dose wall motion score) and digoxin use in follow-up are also independent predictors and add incremental prognostic value to ejection fraction improvement.

Incremental prognostic value of echocardiography in patients with prior mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: Patients with prior mitral valve surgery are at increased risk for events late after surgery. The study aim was to investigate the value of assessing clinical variables, and left and right heart anatomy and function, to predict outcome in these patients. METHODS: Two-dimensional echocardiography, Doppler echocardiography and tissue Doppler imaging (TDI) were performed in 84 patients at a mean of 7.3 +/- 7.1 years after mitral valve surgery. The left ventricular ejection fraction (LVEF) was 50 +/- 15%, and 30% of patients were in NYHA class III/IV (congestive heart failure; CHF). Follow up was obtained for events that included repeat mitral or tricuspid valve surgery, and death. RESULTS: During a follow up period of 4.3 +/- 2.0 years, 28 patients suffered events, the univariate clinical predictors of which were NYHA class, calcium antagonist therapy, hyperlipidemia, and tobacco smoking. Left heart predictors included the mean mitral valve gradient (MMVG), left atrial volume index, and lateral wall TDI systolic velocity. Right heart predictors were atrial and right ventricular (RV) dimensions, RV systolic pressure, tricuspid regurgitation (TR) severity, RV free wall TDI E-velocity and E/e' ratio. Multivariate analysis showed that NYHA class (p = 0.02; RR 1.8 (1.1-2.9)), MMVG (p < 0.001; RR 1.16 (1.08-1.24)) and RV dimensions (p = 0.001; RR = 3.2 (1.7-6.2)) were independent predictors of events. A step-wise analysis of independent predictors showed that MMVG added an incremental value to NYHA class (p = 0.003), while RV size added additional value (p = 0.007) to the combination of NYHA class and MMVG. CONCLUSION: Echocardiographic assessments of the left and right heart can add significant prognostic value to the clinical assessment of patients after mitral valve surgery.

Prognostic value of left atrial size in hypertensive African Americans undergoing stress echocardiography.

BACKGROUND: Left atrial (LA) enlargement is a marker of increased risk in the general population undergoing stress echocardiography. African American (AA) patients with hypertension are known to have less atrial remodeling than whites with hypertension. The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain. AIM: To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography. METHODS: This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period. Clinical characteristics including cardiovascular risk factors, stress and echocardiographic data were collected from the electronic health record of a large community hospital. Treadmill exercise and Dobutamine protocols were conducted based on standard practices. Patients were followed for all-cause mortality. The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis. Cox regression was used to determine variables associated with outcome. RESULTS: The mean age was 57 ± 12 years. LA dilatation was present in 9% (54) of patients (LA anteroposterior ≥ 2.4 cm/m2). There were 85 deaths (15%) during 4.5 ± 1.7 years of follow-up. LA diameter indexed for body surface area had an area under the curve of 0.72 ± 0.03 (optimal cut-point of 2.05 cm/m2). Variables independently associated with mortality included age [P = 0.004, hazard ratio (HR) 1.34 (1.10-1.64)], tobacco use [P = 0.001, HR 2.59 (1.51-4.44)], left ventricular hypertrophy [P = 0.001 , HR 2.14 (1.35-3.39)], Dobutamine stress [P = 0.003, HR 2.12 (1.29-3.47)], heart failure history [P = 0.031, HR 1.76 (1.05-2.94)], LA diameter ≥ 2.05 cm/m2 [P = 0.027, HR 1.73 (1.06-2.82)], and an abnormal stress echocardiogram [P = 0.033, HR 1.67 (1.04-2.68)]. LA diameter as a continuous variable was also independently associated with mortality but LA size ≥ 2.40 cm/m2 was not. CONCLUSION: LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used. LA enlargement is independently associated with mortality when a lower than "normal" threshold (≥ 2.05 cm/m2) is used.

Feasibility of using real time "Live 3D" echocardiography to visualize the stenotic aortic valve.

BACKGROUND: Aortic stenosis valve area (AS AVA) using the continuity equation (CE AVA) has limitations. Thus anatomic assessment of AS AVA would be useful. METHOD: AS AVA was measured using "live three-dimensional (3D)" echocardiography that is a two-dimensional (2D) display of a three-dimensionally acquired 2-3 cm thick pyramidal image. In 52 aortic stenosis patients with CE AVA measurements, attempts were made at measuring AS AVA using 2D echocardiography (2D AVA) and real time, Live 3D echocardiography (3D AVA). 3D AVA and 2D AVA were compared to each other and to CE AVA. RESULTS: 2D AVA could be obtained in 30 patients (58%) and 3D AVA in 50 patients (96%). Of the 30 patients in whom 3D AVA and 2D AVA were both measured, the correlation was 0.831 (P < 0.001). 3D AVA was smaller in 19 patients. In 17 of these patients, 3D AVA was closer to CE AVA. In two patients, 2D AVA was smaller than 3D AVA and in both patients 3D AVA was closer to CE AVA. The correlations between 2D AVA and CE AVA and 3D AVA and CE AVA were 0.581 and 0.673, respectively (all P < 0.001). CONCLUSION: A simplified 3D technique that is a "thick slice" 2D examination, can obtain AS AVA more often than a "thin slice" 2D echocardiogram. This 3D AVA correlates well with 2D AVA but is smaller and correlates better with CE AVA suggesting that the effective AS orifice is not planar but is more of a "tunnel" than a "flat ring."

Evaluation of the anti-ischemic effects of D-ribose during dobutamine stress echocardiography: a pilot study.

D-Ribose, a pentose sugar, has shown to improve myocardial high-energy phosphate stores depleted by ischemia. This study investigated the ability of D-Ribose with low dose dobutamine to improve the contractile response of viable myocardium to dobutamine and to assess the efficacy of D-ribose in reducing stress-induced ischemia. Twenty-six patients with ischemic cardiomyopathy completed a two-day, randomized, double blind crossover trial comparing the effects of D-Ribose and placebo on regional wall motion. On the first study day, either D-Ribose or placebo was infused for 4.5 hours. Low (5 and 10 micro/kg/min) and subsequently, high (up to 50 micro/kg/min) dose dobutamine echocardiography was then performed. On the second study day, patients crossed over to the alternative article for a similar 4.5 hours infusion time period and underwent a similar evaluation. The wall motion response during low dose dobutamine was the same with D-Ribose and placebo in 77% of segments (203/263, Kappa = 0.37). In segments with discordant responses, more segments improved with D-Ribose than with placebo (41 vs. 19 segments, p = 0.006). With high dose dobutamine infusion, the wall motion response (ischemia vs. no ischemia) was the same with D-Ribose and placebo in 83% of interpretable segments (301/363, kappa = 0.244). In segments with discordant responses, there were more ischemic segments with placebo compared to D-Ribose (36 vs. 26, p = 0.253). Nineteen patients developed ischemia during the dobutamine and placebo infusion and 13 patients had ischemia during dobutamine and D-ribose infusion (p = 0.109). D-Ribose improved contractile responses to dobutamine in viable myocardium with resting dysfunction but had no significant effect in reducing the frequency of stress-induced wall motion abnormalities.

Clinical assessment and rest and stress echocardiography for prediction of long-term prognosis in African Americans with known or suspected coronary artery disease.

BACKGROUND: There is limited information on noninvasive risk stratification of African Americans, a high-risk group for cardiovascular events. We investigated the value of clinical assessment and echocardiography for the prediction of a long-term prognosis in African Americans. METHODS: Dobutamine echocardiography was performed in 324 African Americans. Two-dimensional measurements were performed at rest, and rest and stress wall motion was assessed. A retrospective follow-up was conducted for cardiac events: myocardial infarction (MI) or cardiac death (CD). RESULTS: The mean age was 59 +/- 12 years, and 83% of patients had hypertension. The follow-up was obtained in 318 (98%) patients for a mean of 5.3 years. The events occurred in 107 (33%) subjects. The independent predictors of events were history of MI (P = 0.001, risk ratio [RR] 2.04), ischemia (P = 0.007, RR 1.97), fractional shortening (P = 0.033, RR 0.08), and left atrial (LA) dimension (P = 0.034, RR 1.39). An LA size of 3.6 cm and a fractional shortening of 0.30 were the best cutoff values for the prediction of events. Prior MI, ischemia, LA size >3.6 cm, and fractional shortening <0.30 were each considered independent risk predictors for events. The event rates were 13%, 21%, 38%, 59%, and 57% in patients with 0, 1, 2, 3, and 4 risk predictors, respectively. Event-free survival progressively worsened with an increasing number of predictors: 0 or 1 versus 2 predictors, P < 0.001; 2 versus 3 or 4 predictors, P = 0.003. CONCLUSION: The long-term prognosis of African Americans can be accurately predicted by clinical assessment combined with rest and stress echocardiography.

Low dose wall motion score predicts the short and long-term benefit of surgical revascularization in patients with ischemic left ventricular dysfunction.

We investigated the influence of the extent of viability using low dose dobutamine wall motion score index (WMS) on the survival benefit of surgical revascularization (CABG) versus medical therapy. In the STICH trial, viability assessment was not helpful in determining the benefit of CABG. However, the extent of viable myocardium with contractile function was not assessed in the trial. Dobutamine echocardiography was performed in 250 patients with ischemic left ventricular dysfunction (125-medically treated, 125-CABG). The mean ejection fraction (EF) was 32% in both groups. WMS during low dose dobutamine infusion was used to classify patients into groups with extensive (WMS < 2.00), intermediate (WMS 2.00-2.49), and limited (WMS ≥ 2.50) viability. Survival free of cardiac death was assessed at 2 years and for the complete duration of follow-up. There were 44 (35.2%) and 67 (53.6%) cardiac deaths in the revascularized and medically treated patients respectively (follow-up of 5.7 ± 5.8 years). Revascularized and medically treated patients with extensive viability had similar 2-year survival (p = 0.567) but revascularized patients had improved long-term survival (p = 0.0001). In those with intermediate viability, revascularization improved both 2 year (p = 0.014) and long-term survival (p = 0.0001). In patients with limited viability, 2-year survival was worse in revascularized patients (p = 0.04) and long-term survival was similar (p = 0 .25) in revascularized and medically treated groups. Patients with extensive and intermediate amounts of viability have improved survival with CABG but those with limited viability have poorer short-term outcome and no long-term benefit.

Diagnostic Performance of Dobutamine Stress Echocardiography in End-Stage Liver Disease.

OBJECTIVES: This study determined the test performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD). BACKGROUND: The reported sensitivity of DSE in ESLD has been variable. METHODS: Data from 633 ESLD patients who had coronary angiography within 6 months after DSE was analyzed. RESULTS: The prevalence of coronary arterial disease (CAD) (≥70% stenosis by quantitative angiography) was 12% (74 of 633 patients). DSE sensitivity was 24% (17 of 72 patients), and specificity was 90% (503 of 559 patients). The positive and negative predictive values were 23% (17 of 73 patients) and 90% (503 of 558 patients), respectively. Stratifying the cohort into low-, intermediate-, and high-risk CAD groups yielded sensitivities of 0%, 21%, and 32%, respectively. Independent predictors of an accurate ischemic DSE result included left ventricular internal dimension at end-diastole (LVIDd) >4.8 cm and assigning ischemia based on tardokinesis or lack of low-to-peak dose hyperkinesis (p < 0.05 for all). DSE sensitivity was 38% in LVIDd >4.8 cm versus 13% with LVIDd ≤4.8 cm (p = 0.013). The sensitivity was 67% when tardokinesis or lack of hyperkinesis was considered abnormal versus 15% (p < 0.001) for readings that did not consider tardokinesis or lack of hyperkinesis abnormal. There was a higher frequency of cardiac events in patients with significant CAD who had abnormal (45%) versus normal (18%) DSE (p = 0.01). CONCLUSIONS: The sensitivity of DSE in ESLD was low. DSE sensitivity was higher for those with larger cavity dimension and when tardokinesis or lack of hyperkinesis was considered abnormal. An abnormal DSE in those with significant CAD was associated with worse outcome.

Assessing prognosis in patients with diabetes mellitus--the Achilles' heel of cardiac stress imaging tests?

The prognostic utility of stress imaging studies has been validated in numerous studies and, in general, patients with a normal imaging study have annual cardiac ischemic event rates of <1%. However, this predictive value of a normal stress imaging study does not appear to be applicable to subjects with diabetes. In this editorial, we summarize the current available data on prognostic utility of stress imaging studies in subjects with diabetes and provide insights into how to interpret and integrate these data for daily clinical practice. In conclusion, currently available data suggest that the prognostic value of stress imaging studies in subjects with diabetes differs from those without diabetes and should be interpreted as such.

Safety and efficacy of a TTR specific antisense oligonucleotide in patients with transthyretin amyloid cardiomyopathy.

OBJECTIVES: Cardiomyopathy is a major cause of death in both the hereditary form of transthyretin (TTR) amyloidosis and the sporadic late-age-onset transthyretin amyloidosis (ATTR wild-type (ATTRwt)). Clinically disease progression from time of diagnosis to death is usually quoted as 5- to 15-years. In prior studies, significant progression of cardiac parameters in patients with moderate to severe cardiomyopathy has been noted within a 12-month time span. METHODS: The present study was designed to prospectively monitor changes in cardiac parameters, both structural and functional, in patients with ATTR cardiomyopathy while treated with a TTR specific antisense oligonucleotide (ASO; IONIS-TTR℞) designed to lower blood levels of the amyloid fibril precursor protein. To date 22 patients have been admitted to the study, 15 have completed 12 months on the drug and are the subject of this report. RESULTS: Eight patients with hereditary ATTR amyloidosis and 7 patients with wild-type ATTR amyloidosis with moderate to severely advanced restrictive cardiomyopathy showed stabilization of disease as measured by left ventricular wall thickness, left ventricular mass (LVM), 6-min walk test (6MWT), and echocardiographic global systolic strain. IONIS-TTR℞ was well tolerated by all 15 subjects and showed a good safety profile. CONCLUSIONS: ASO treatment of patients with moderate to advanced ATTR cardiomyopathy shows indication of stabilization of disease progression and may therefore contribute to enhanced life expectancy.

Prognostic importance of wall motion abnormalities in patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator.

Patients with extensive regional wall motion abnormalities are predisposed to development of ventricular tachyarrhythmia. The prognostic effect of this in patients with an implantable cardioverter-defibrillator (ICD) and coronary artery disease (CAD) is not known. Echocardiographic left ventricular systolic indexes, wall motion score index (WMSI), and extent of regional akinesia in 140 patients (65 +/- 10 years old; 92% men) with an ICD and CAD were studied. Arrhythmic events requiring ICD therapy and causing death (n = 41, 29%) were recorded over a mean follow-up of 1.4 +/- 0.8 years. Left ventricular basal fractional shortening, ejection fraction, global WMSI, and extent of akinesia, especially in the inferoposterior regions of a right coronary artery territory, were univariate predictors (all p values <0.05). Global WMSI (hazard ratio 2.18, 95% confidence interval 1.03 to 4.65, p = 0.04) and fractional shortening (hazard ratio 0.93, 95% confidence interval 0.88 to 1.00, p = 0.04) were multivariate predictors. Global WMSI (p = 0.04) and > or =2 right coronary region akinetic segments (p = 0.05) provided incremental risk prediction to left ventricular ejection fraction in a global risk-assessment model (chi-square p = 0.001). Presence of right coronary region akinesia better identified those at increased risk of events (p = 0.02) compared with the presence of left anterior descending region akinesia (p = 0.2), independent of systolic function. In conclusion, global WMSI and left ventricular basal fractional shortening were important additional risk predictors of ICD events in CAD. Global WMSI and right coronary region inferoposterior akinesia provided independent and incremental risk assessment to left ventricular ejection fraction and improved identification of those at increased risk of ICD-related events in patients with ischemic cardiomyopathy.

Prognostic utility of blood pressure-adjusted global and basal systolic longitudinal strain.

Assessment of global longitudinal systolic strain (GLS) and longitudinal systolic strain of the basal segments (BLS) has shown prognostic value in cardiac disorders. However, strain is reduced with increased afterload. We assessed the prognostic value of GLS and BLS adjusted for afterload. GLS and BLS were determined in 272 subjects with normal ejection fraction and no known coronary disease, or significant valve disease. Systolic blood pressure (SP) and diastolic blood pressure (DP) obtained at the time of echocardiography were used to adjust GLS and BLS as follows: strain×SP (mmHg)/120 mmHg and strain×DP (mmHg)/80 mmHg. Patients were followed for cardiac events and mortality. The mean age was 53±15 years and 53% had hypertension. There were 19 cardiac events and 70 deaths over a mean follow-up of 26±14 months. Cox analysis showed that left ventricular mass index (P=0.001), BLS (P<0.001), and DP-adjusted BLS (P<0.001) were independent predictors of cardiac events. DP-adjusted BLS added incremental value (P<0.001) to the other two predictors and had an area under the curve of 0.838 for events. DP (P=0.001), age (P=0.001), ACE inhibitor use (P=0.017), and SP-adjusted BLS (P=0.012) were independent predictors of mortality. SP-adjusted BLS added incremental value (P=0.014) to the other independent predictors. In conclusion, DP-adjusted BLS and SP-adjusted BLS were independent predictors of cardiac events and mortality, respectively. Blood pressure-adjusted strain added incremental prognostic value to other predictors of outcome.

Incremental value of myocardial viability for prediction of long-term prognosis in surgically revascularized patients with left ventricular dysfunction.

OBJECTIVES: We assessed the incremental long-term prognostic value of myocardial viability in surgically revascularized (CABG) patients with left ventricular (LV) dysfunction. BACKGROUND: Clinical factors, medical therapy, the degree of LV dysfunction, and stress-induced ischemia may affect the relative prognostic value of myocardial viability. METHODS: Patients with coronary disease and ventricular dysfunction (mean ejection fraction 33% by echocardiography, 25% by angiography) were studied with dobutamine echocardiography. Follow-up (mean -4.9 years) was obtained in 95 patients (85% triple-vessel disease) who underwent CABG. RESULTS: The use of angiotensin-converting enzyme inhibitors, advanced heart failure, rest, low- and peak-dose wall motion scores were univariate predictors of cardiac death. The extent of contractile reserve and ischemia were not predictive. Low-dose score was the strongest multivariate predictor of death (p < 0.001, hazard ratio 6.7). A biphasic response predicted better survival (p = 0.045, hazard ratio 0.5). Five-year survival was better in those with extensive (low-dose score <2.00) versus intermediate (score 2.00 to 2.49) amounts of viable myocardium (p = 0.019). Patients with the least viability (score > or =2.5) had the worst outcome (p = 0.0001 vs. those with low-dose score <2.00; p = 0.05 vs. those with score 2.00 to 2.49). In stepwise multivariate analysis, low-dose score added incremental prognostic value (p = 0.024) to clinical information and rest score. CONCLUSIONS: Low-dose score, representing the extent of viable myocardium, has incremental prognostic value as a predictor of long-term outcome in CABG patients with LV dysfunction.