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1.
Nat Med ; 27(11): 1954-1960, 2021 11.
Article En | MEDLINE | ID: mdl-34711976

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.


Benzhydryl Compounds/therapeutic use , Glucosides/therapeutic use , Heart Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2/drug effects , Stroke Volume/drug effects , Aged , Benzhydryl Compounds/adverse effects , Double-Blind Method , Exercise/physiology , Female , Glucosides/adverse effects , Health Status , Humans , Male , Middle Aged , Placebos/administration & dosage , Quality of Life/psychology , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Surveys and Questionnaires
2.
J Cancer Res Ther ; 9(3): 490-2, 2013.
Article En | MEDLINE | ID: mdl-24125989

Cardiac metastasis in thyroid cancer is extremely rare. Iodine-131-d whole-body scan has been used widely to detect thyroid metastasis. However, in dedifferentiated cases, iodine scan has low diagnostic value particularly for diagnosing cardiac metastasis. In the absence of (131)I uptake, (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) can be used as an alternative and has a high sensitivity for thyroid metastasis, but still low sensitivity for cardiac metastasis. Therefore, meticulous attention to the pattern of uptake and comparison with patients' previous studies is critical. Additionally, cardiac magnetic resonance imaging (MRI) can provide additional and critical information.


Carcinoma/pathology , Heart Neoplasms/secondary , Heart Ventricles/pathology , Thyroid Neoplasms/pathology , Aged , Carcinoma/diagnosis , Carcinoma, Papillary , Echocardiography , Heart Neoplasms/diagnosis , Humans , Male , Positron-Emission Tomography , Thyroid Cancer, Papillary , Thyroid Neoplasms/diagnosis , Tomography, X-Ray Computed
4.
Circ Heart Fail ; 3(6): 706-14, 2010 Nov.
Article En | MEDLINE | ID: mdl-20798278

BACKGROUND: We sought to assess the predictive value of the Seattle Heart Failure Model (SHFM) when applied to ambulatory patients with advanced heart failure (HF) presented to an advanced HF therapeutics committee at a tertiary care US institution. METHODS AND RESULTS: We evaluated model discrimination and calibration in 215 consecutive ambulatory patients who were presented to the Cleveland Clinic advanced HF therapeutics committee between 2004 to 2007 for evaluation for advanced options including transplantation and ventricular assist device (VAD). Analyses were stratified by committee decision (not listed versus listed United Network of Organ Sharing [UNOS] Status 2). Eighty-five percent had 1 or no missing SHFM variables. The primary outcome was a composite of all-cause mortality, VAD, or urgent (UNOS Status 1) transplantation. During a median follow-up of 24 months, 68 died, 18 received VAD support, and 81 underwent heart transplantation. Discrimination was modest both for those not listed (c-index, 0.683 at 1 year and 0.648 at 2 years), and for those listed UNOS status 2 (c-index, 0.629 at 1 year and 0.628 at 2 years). Calibration was acceptable among those patients not listed for heart transplantation but with substantial underestimation of risk (ie, overestimation of survival free of VAD or urgent transplantation) among UNOS status 2 patients. CONCLUSIONS: In ambulatory patients presented to an advanced HF therapeutics committee for evaluation for heart transplantation, the SHFM offers modest discrimination of risk for the primary composite outcome of mortality, VAD, or urgent transplantation, with underestimation of risk in those patients listed for nonurgent transplantation. Interpretation of risk prediction by the SHFM in this patient population must be done with caution.


Academic Medical Centers , Heart Failure/physiopathology , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Outpatients , Pharmacy and Therapeutics Committee , Calibration , Disease Progression , Female , Follow-Up Studies , Heart Failure/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Models, Statistical , Prognosis , Risk Assessment/methods
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