Long-term cardiac surveillance and outcomes of COVID-19 patients.

Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms.

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. METHODS: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion. RESULTS: No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy. CONCLUSION: Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: CRATUS (#NCT02065245).

Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study).

RATIONALE: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure. OBJECTIVE: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.5 cc per injection × 10 injections per patient). Patients were followed for 12 months for safety and efficacy end points. There were no treatment-emergent serious adverse events at 30 days or treatment-related serious adverse events at 12 months. The Major Adverse Cardiac Event rate was 20.0% (95% confidence interval [CI], 6.9% to 50.0%) in 20 million and 13.3% (95% CI, 3.5% to 43.6%) in 100 million (P=0.58). Worsening heart failure rehospitalization was 20.0% (95% CI, 6.9% to 50.0%) in 20 million and 7.1% (95% CI, 1.0% to 40.9%) in 100 million (P=0.27). Whereas scar size reduced to a similar degree in both groups: 20 million by -6.4 g (interquartile range, -13.5 to -3.4 g; P=0.001) and 100 million by -6.1 g (interquartile range, -8.1 to -4.6 g; P=0.0002), the ejection fraction improved only with 100 million by 3.7 U (interquartile range, 1.1 to 6.1; P=0.04). New York Heart Association class improved at 12 months in 35.7% (95% CI, 12.7% to 64.9%) in 20 million and 42.9% (95% CI, 17.7% to 71.1%) in 100 million. Importantly, proBNP (pro-brain natriuretic peptide) increased at 12 months in 20 million by 0.32 log pg/mL (95% CI, 0.02 to 0.62; P=0.039), but not in 100 million (-0.07 log pg/mL; 95% CI, -0.36 to 0.23; P=0.65; between group P=0.07). CONCLUSIONS: Although both cell doses reduced scar size, only the 100 million dose increased ejection fraction. This study highlights the crucial role of cell dose in the responses to cell therapy. Determining optimal dose and delivery is essential to advance the field, decipher mechanism(s) of action and enhance planning of pivotal Phase III trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02013674.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

BACKGROUND: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty. METHODS: In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The primary endpoint was incidence of any treatment-emergent serious adverse events measured at 1 month postinfusion. The secondary endpoints were functional efficacy domains and inflammatory biomarkers, measured at 3 and 6 months, respectively. RESULTS: There were no treatment-emergent serious adverse events at 1-month postinfusion or significant donor-specific immune reactions during the first 6 months. There was one death at 258 days postinfusion in the 200-million group. In all treatment groups, 6-minute walk distance increased at 3 months (p = .02) and 6 months (p = .001) and TNF-α levels decreased at 6 months (p < .0001). Overall, the 100-million dose showed the best improvement in all parameters, with the exception of TNF-α, which showed an improvement in both the 100- and 200-million groups (p = .0001 and p = .0001, respectively). The 100-million cell-dose group also showed significant improvements in the physical component of the SF-36 quality of life assessment at all time points relative to baseline. CONCLUSIONS: Allo-hMSCs are safe and immunologically tolerated in aging frailty patients. Improvements in functional and immunologic status suggest that ongoing clinical development of cell-based therapy is warranted for frailty.

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial.

BACKGROUND: Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). OBJECTIVES: The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. METHODS: Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. RESULTS: There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). CONCLUSIONS: These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625).

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial.

RATIONALE: Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis. OBJECTIVE: To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects. METHODS AND RESULTS: Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 ± 1.7%, P=0.0002) and decreased scar mass (-47.5 ± 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 ± 0.07), whereas revascularized (0.5 ± 0.21) and nontreated segments (-0.07 ± 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments). CONCLUSIONS: Intramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.

IMPORTANCE: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS: Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES: Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS: No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE: Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00768066.

Comparison of allogeneic vs autologous bone marrow­derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

CONTEXT: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. OBJECTIVE: To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. DESIGN, SETTING, AND PATIENTS: A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. INTERVENTION: Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. MAIN OUTCOME MEASURES: Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. RESULTS: Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. CONCLUSIONS: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01087996.

Orthodeoxia platypnea syndrome in a patient with lipomatous hypertrophy of the interatrial septum due to long-term steroid use.

We describe an unusual case of orthodeoxia platypnea syndrome exacerbated by right ventricular inflow obstruction due to iatrogenic steroid-induced adipose deposition in cardiac tissues. A 68-year-old man on long-term prednisone therapy for eosinophilic pneumonia presented with progressive dyspnea worsened by bending forward. By using pulse oximetry, he was noted to have positional hypoxemia. Transthoracic echocardiogram demonstrated normal right-sided pressures but severe right to left shunting through a patent foramen ovale. Transesophageal echocardiogram showed a large patent foramen ovale, severe lipomatous hypertrophy of the interatrial septum, and massive adipose deposition in the pericardium causing compression of the right ventricular inflow tract. The patient underwent percutaneous closure of the patent foramen ovale, which resulted in the resolution of symptoms and hypoxemia. This case is unique because long-term steroid use resulted in reverse Lutembacher physiology and clinical orthodeoxia platypnea syndrome by inducing lipomatous hypertrophy of the interatrial septum and compression of the right atrium.

Comprehensive evaluation of Kawasaki disease with electrocardiogram-gated cardiac multidetector computed tomography.

We present a case of a young woman with Kawasaki disease who was comprehensively evaluated by electrocardiograph-gated cardiac multidetector computed tomography (MDCT). MDCT disclosed 3-vessel giant coronary arterial aneurysms and associated focal apical septal myocardial pathology. This was characterized by an early enhancement defect, myocardial thinning, and hypokinesia. These findings are likely due to focal ischemic insult resulting from distal embolization of thrombus material from the giant proximal right coronary arterial aneurysms. This case illustrates the full capabilities of MDCT in the comprehensive evaluation of Kawasaki disease.

Comparison of epicardial and pericardial fat thickness assessed by echocardiography in African American and non-Hispanic White men: a pilot study.

OBJECTIVES: Compared to non-Hispanic Whites, African American men have less intra-abdominal visceral adipose tissue (VAT) relative to total fat mass despite having a higher risk of obesity-related diseases. This study explores whether this racial pattern of VAT distribution extends to the intrathoracic VAT. METHODS: We used two-dimensional transthoracic echocardiography to measure pericardial and maximum and minimum epicardial fat thickness anterior to the right ventricle in 50 African American and 106 non-Hispanic White men, aged 40-75 years, consecutively referred for echocardiography for standard clinical indications. Age, coronary risk factors, height, and weight were recorded, and body mass index (BMI) was calculated. The two groups were compared with respect to pericardial and maximum, minimum, and average epicardial fat thicknesses. RESULTS: Among non-Hispanic Whites, pericardial and minimum epicardial fat measured at the mid-rightventricular wall were higher by 37% and 69%, respectively, than among African Americans (5.2+/-3.1 mm vs 3.8+/-3.1 mm, P<.011; 2.2+/-1.6 mm vs 1.3+/-1.2 mm, P<.001). Maximum epicardial fat along the distal right ventricular wall was 19% greater in non-Hispanic Whites, but this difference was not statistically significant (4.3+/-2.6 mm vs 3.6+/-2.0 mm, P=.133). The average epicardial fat measured at two sites was 26% greater in non-Hispanic Whites (2.9+/-2.0 mm vs 2.3+/-1.3 mm, P=.019). CONCLUSIONS: Among men referred for echocardiography, non-Hispanic Whites have more epicardial and pericardial fat than do African Americans. Echocardiography may be a useful research tool for investigating VAT distribution and its relationship to cardiovascular risk.

Effects of age and pulmonary arterial hypertension on the different phases of right atrial function.

To evaluate the effects of age and pulmonary hypertension on phasic right atrial function we measured right atrial volumes at 3 different points in the cardiac cycle in 57 healthy subjects and 33 patients with pulmonary arterial hypertension. Right atrial reservoir function was assessed by systolic filling volume and passive and active emptying by passive and active emptying volume and fraction of total emptying. We compared these phases of right atrial function in 30 healthy subjects <60 and 27 > or = 60 years old, and in a separate analysis, in 33 patients with pulmonary arterial hypertension and 33 matched controls. Healthy subjects > or =60 years had lower passive emptying fraction (46.0 +/- 23.3% vs 59.9 +/- 15.4%, P = 0.011) and larger active emptying volume (7.0 +/- 3.5 vs 4.9 +/- 2.5 ml/m2, P = 0.013 ) and fraction (54.0 +/- 23.3% vs 40.1 +/- 15.4%, P = 0.011) compared to those <60. Patients with pulmonary arterial hypertension had larger right atrial volumes, systolic filling volume (18.3 +/- 6.9 vs 12.3 +/- 4.9 ml/m2, P < or = 0.001) and active emptying volume and fraction (11.2 +/- 6.9 vs 5.4 +/- 3.0 ml/m2, P < or = 0.001; 60.7 +/- 29.9 vs 44.9 +/- 19.0%, P = 0.017 ) and smaller passive emptying fraction (39.3 +/- 29.9% vs 55.1 +/- 19.0%, P = 0.017) compared to controls. Aging and pulmonary arterial hypertension are associated with a decrease in passive right atrial emptying and an increase in right atrial active emptying.

Effects of weight loss after gastric bypass on right and left ventricular function assessed by tissue Doppler imaging.

To evaluate the effects of substantial weight loss on tissue Doppler imaging parameters of right ventricular (RV) and left ventricular (LV) systolic and diastolic function, we performed standard echocardiography and tissue Doppler imaging in 17 patients with severe obesity before and after gastric bypass. Patients lost 39 +/- 10 kg over 7.6 +/- 3.6 months. Adjusted LV mass decreased (134 +/- 41 to 119 +/- 31 kg/m, p = 0.031). After weight loss, the ratios of early-to-late diastolic mitral and tricuspid inflow velocities increased (1.3 +/- 0.2 to 1.6 +/- 0.5, p = 0.02; 1.0 +/- 0.1 to 1.6 +/- 0.3, p = 0.003). Early diastolic tissue Doppler velocities increased at both the lateral and septal mitral annulus (7.6 +/- 1.5 to 9.3 +/- 2.5 cm/s, p = 0.009; and 6.6 +/- 1.4 to 7.7 +/- 1.7 cm/s; p = 0.028, respectively) and for their 2-site average (7.2 +/- 1.0 to 8.5 +/- 1.7 cm/s, p = 0.007). Early diastolic tricuspid annular velocity increased (7.2 +/- 2.8 to 10.6 +/- 2.3 cm/s, p <0.001) as did the ratio of early-to-late tricuspid annular diastolic velocity (0.9 +/- 0.4 to 1.1 +/- 0.2, p = 0.038). Tricuspid annular systolic velocity increased (8.6 +/- 2.5 to 10.3 +/- 2.7 cm/s, p = 0.037). In patients with severe obesity, significant weight loss results in an increase in tricuspid annular systolic and early diastolic velocities and mitral annular early diastolic velocities.

Tissue Doppler imaging of the right and left ventricle in severe obesity (body mass index >35 kg/m2).

We investigated right and left heart function in 51 patients with a body mass index of >35 kg/m(2) who underwent evaluation for gastric bypass surgery using standard Doppler echocardiography and color tissue Doppler imaging. Left atrial diameter (3.7 +/- 0.5 vs 3.3 +/- 0.4 cm, p <0.001), left ventricular end-diastolic diameter (5.0 +/- 0.6 vs 4.5 +/- 0.4 cm, p <0.001), and left ventricular mass index (119 +/- 49 vs 76 +/- 26 g/m, p <0.001) were increased in patients with severe obesity. Early diastolic mitral annular velocity (7.5 +/- 2.1 vs 9.6 +/- 3.0 cm/s, p <0.001), early diastolic/late diastolic mitral annular velocity ratio (1.38 +/- 0.6 vs 1.94 +/- 1.3, p = 0.007), early diastolic tricuspid annular velocity (7.8 +/- 2.6 vs 9.5 +/- 2.4 cm/s, p = 0.002), early diastolic/late diastolic tricuspid annular velocity ratio (0.9 +/- 0.36 vs 1.1 +/- 0.4, p = 0.048), and mitral annular systolic velocity (5.7 +/- 1.3 vs 6.5 +/- 1.5 cm/s, p = 0.012) were significantly lower in obese patients. Early diastolic mitral inflow/mitral annular velocity ratio was increased in the obese (13.5 +/- 4.7 vs 9.1 +/- 3.6, p <0.001). Tricuspid annular systolic velocities did not differ.

Rapid resolution of left ventricular thrombus in antiphospholipid syndrome.

A 43-year-old male with recurrent cerebral infarctions and high titers of antiphospholipid antibodies was found to have a thrombus in his left ventricular outflow tract by transthoracic echocardiography. This thrombus disappeared after less than 24 hours of intravenous heparin therapy due to resolution or asymptomatic embolism. Left ventricular thrombi in patients with antiphospholipid syndrome and rapid disappearance of left ventricular thrombi with heparin therapy are infrequently reported occurrences.

Noncompaction of the ventricular myocardium: the use of contrast-enhanced echocardiography in diagnosis.

We describe a case of noncompaction of the ventricular myocardium diagnosed in the preoperative evaluation of a patient undergoing renal transplantation. Ventricular noncompaction is characterized by numerous prominent trabecular recesses with intratrabecular blood from the ventricular cavity. Color Doppler was suggestive of intramyocardial flow. With contrast-enhanced echocardiography the endocardial borders were clearly demarcated, allowing for visualization of trabecular recesses and intratrabecular flow. Contrast-enhanced echocardiography facilitates the diagnosis of noncompaction of the ventricular myocardium, circumventing the need for invasive diagnostic testing.

Effect of estrogen plus progestin on progression of carotid atherosclerosis in postmenopausal women with heart disease: HERS B-mode substudy.

OBJECTIVE: The Heart and Estrogen/Progestin Replacement Study (HERS) found no overall effect of estrogen plus progestin (compared with placebo) on coronary event rates in 2763 postmenopausal women with established coronary disease (mean 4.1 years of follow-up). In addition to the events trial, a carotid ultrasound substudy was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process. METHODS AND RESULTS: Within the larger HERS, a subset of 362 participants underwent carotid B-mode ultrasound examinations at baseline and the end of follow-up. Progression of carotid atherosclerosis was measured as the temporal change in intimal-medial thickness (IMT). CONCLUSIONS: IMT progressed in the hormone treatment and placebo groups, although there was no statistical difference between the rates: IMT progressed 26 microm/y (95% CI 18 to 34 microm/y) in the hormone group and 31 microm/y (95% CI 21 to 40 microm/y) in the placebo group (P=0.44). There were also no significant treatment effects when the results were examined by carotid segment or were adjusted for covariates. These data support the American Heart Association recommendation that women with established coronary disease should not initiate hormone therapy with an expectation of atherosclerotic benefit.

Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).

CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized trial of estrogen plus progestin therapy after menopause. OBJECTIVE: To examine the effect of long-term postmenopausal hormone therapy on common noncardiovascular disease outcomes. DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent open-label observational follow-up for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 postmenopausal women with coronary disease and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group and increased from 0% (year 1) to 8% (year 6) in the placebo group. MAIN OUTCOME MEASURES: Thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality. RESULTS: Comparing women assigned to hormone therapy with those assigned to placebo, the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and 3 of the 73 women with thromboembolism died within 30 days due to pulmonary embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses did not alter our conclusions. CONCLUSIONS: Treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery. Trends in other disease outcomes were not favorable and should be assessed in larger trials and in broader populations.