Research Spotlight

Roberts, W. C., M. Moore, J. M. Ko and B. L. Hamman (2016). “Mitral valve replacement after failed mitral ring insertion with or without leaflet/chordal repair for pure mitral regurgitation.” Am J Cardiol 117(11): 1790-1807.

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Mitral repair operations for correction of pure mitral regurgitation (MR) are generally quite successful. Occasionally, however, the reparative procedure incompletely corrects the MR or the MR recurs. From March 1993 to January 2016, twenty nine patients had mitral valve replacement after the initial mitral repair operation, and observations in them were analyzed. All 29 patients at the repair operation had an annular ring inserted and later (<1 year in 6 and >1 year in 21) mitral valve replacement. The cause of the MR before the repair operation appears to have been prolapse in 16 patients (55%), secondary (functional) in 12 (41%) (ischemic in 5), and infective endocarditis which healed in 1 (3%). At the replacement operation the excised anterior mitral leaflet was thickened in all 29 patients. Some degree of stenosis appeared to have been present in 16 of the 29 patients before the replacement operation, although only 10 had an echocardiographic or hemodynamic recording of a transvalvular gradient; at least 11 patients had restricted motion of the posterior mitral leaflet; 10, ring dehiscence; 2, severe hemolysis; and 2, left ventricular outflow obstruction. In conclusion, there are multiple reasons for valve replacement after earlier mitral repair. Uniformly, at the time of the replacement, the mitral leaflets were thickened by fibrous tissue. Measurement of the area enclosed by the 360 degrees rings and study of the excised leaflet suggest that the ring itself may have contributed to the leaflet scarring and development of some transmitral stenosis.

Palazzuoli, A., G. Ruocco, M. Pellegrini, M. Beltrami, N. Giordano, R. Nuti and P. A. McCullough (2016). “Prognostic significance of hyperuricemia in patients with acute heart failure.” Am J Cardiol 117(10): 1616-1621.

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Serum uric acid (UA) is associated with death and hospitalization in chronic heart failure (HF). However, UA in acute HF has not been well studied with respect to its relation to renal dysfunction and vascular congestion. We measured admission serum UA along with baseline variables in 281 patients with acute HF screened from the Loop Diuretics Administration and Acute Heart Failure (Diur-HF) trial. Hyperuricemia was defined as serum UA >7 mg/dl in men and >6 mg/dl in women. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2) before hospital admission. Death or HF hospitalization at 6 months was the primary outcome. The mean UA concentration was 6.4 +/- 2.5 mg/dl, and 121 patients (43.1%) were classified as hyperuricemic. UA values were significantly increased in patients with CKD compared to patients without CKD (6.8 +/- 2.7 vs 6.1 +/- 2.1 mg/dl; p = 0.02); however, UA was not associated with the development of acute kidney injury. Patients with hyperuricemia had greater degrees of pulmonary and systemic congestion than normouricemic patients (congestion score 3.5 vs 2.1, p <0.01). Hyperuricemia was associated with higher risk of death or HF rehospitalization (univariate hazard ratio 1.46 [1.02 to 2.10]; p = 0.04, multivariate hazard ratio 1.69 [1.16 to 2.45]; p = 0.005). In conclusion, hospitalized patients with acute HF, elevated UA levels were associated with both CKD and pulmonary congestion. After controlling for potential confounders, hyperuricemia was associated with rehospitalization and death at 6 months.

Kotecha, D., L. Manzano, H. Krum, G. Rosano, J. Holmes, D. G. Altman, P. D. Collins, M. Packer, J. Wikstrand, A. J. Coats, J. G. Cleland, P. Kirchhof, T. G. von Lueder, A. S. Rigby, B. Andersson, G. Y. Lip, D. J. van Veldhuisen, M. C. Shibata, H. Wedel, M. Bohm and M. D. Flather (2016). “Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: Individual patient data meta-analysis.” Bmj 353: i1855.

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OBJECTIVES: To determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. PARTICIPANTS: 13 833 patients from 11 trials; median age 64; 24% women. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. RESULTS: Compared with placebo, beta blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by beta blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give beta blockers, 15.6% in those receiving placebo). CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive beta blockers to reduce the risk of death and admission to hospital.

Hamilton, R., S. Driver, S. Noorani, L. Callender, M. Bennett and K. Monden (2016). “Utilization and access to healthcare services among community-dwelling people living with spinal cord injury.” J Spinal Cord Med: May 2016 [Epub ahead of print].

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OBJECTIVE: Describe the utilization, accessibility, and satisfaction of primary and preventative health-care services of community-dwelling individuals with spinal cord injury (SCI). DESIGN: Cross sectional, in-person or telephonic survey, utilizing a convenience sample. SETTING: Community. PARTICIPANTS: Individuals with SCI greater than 12-months post injury. INTERVENTIONS: N/A. OUTCOME MEASURES: Demographic, injury related, and 34-item questionnaire of healthcare utilization, accessibility, and satisfaction with services. RESULTS: The final sample consisted of 142 participants (50 female, 92 male). Ninety-nine percent of respondents had a healthcare visit in the past 12-months with primary care physicians (79%), with SCI physiatrists (77%) and urologists (50%) being the most utilized. 43% of the sample reported an ER visit within the past 12-months, with 21% reporting multiple visits. People who visited the ER had completed significantly less secondary education (P = 0.0386) and had a lower estimate of socioeconomic status (P = 0.017). The majority of individuals (66%) were satisfied with their primary care physician and 100% were satisfied with their SCI physiatrist. Individuals who did not visit an SCI physiatrist were significantly more likely to live in a rural area (P = 0.0075), not have private insurance (P = 0.0001), and experience a greater decrease in income post injury (P = 0.010). CONCLUSION: The delivery of care for people with SCI with low socioeconomic status may be remodeled to include patient-centered medical homes where care is directed by an SCI physiatrist. Further increased telehealth efforts would allow for SCI physiatrists to monitor health conditions remotely and focus on preventative treatment.

Gold, R., D. L. Arnold, A. Bar-Or, M. Hutchinson, L. Kappos, E. Havrdova, D. G. MacManus, T. A. Yousry, C. Pozzilli, K. Selmaj, M. T. Sweetser, R. Zhang, M. Yang, J. Potts, M. Novas, D. H. Miller, N. C. Kurukulasuriya, R. J. Fox and T. J. Phillips (2016). “Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of endorse, a randomized extension study.” Mult Scler: May 2016 [Epub ahead of print].

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BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. RESULTS: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. CONCLUSION: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.