Pathophysiology of heart failure and frailty: a common inflammatory origin?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136680/1/acel12581_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136680/2/acel12581.pd

Treatment of Heart Failure with Preserved Ejection Fraction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90240/1/phco.31.3.312.pd

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

Submaximal Oxygen Uptake Kinetics, Functional Mobility, and Physical Activity in Older Adults with Heart Failure and Reduced Ejection Fraction

Background: Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods: Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results: Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions: Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF

Long-term survival in people with transthyretin amyloid cardiomyopathy who took tafamidis: A Plain Language Summary

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results. WHAT DID RESEARCHERS FIND OUT?: In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study. WHAT DO THE RESULTS MEAN?: Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. Clinical Trial Registration: NCT01994889 (ClinicalTrials.gov) Clinical Trial Registration: NCT02791230 (ClinicalTrials.gov)

Galactic-Scale Outflow and Supersonic Ram-Pressure Stripping in the Virgo Cluster Galaxy NGC 4388

The Hawaii Imaging Fabry-Perot Interferometer (HIFI) on the University of Hawaii 2.2m telescope was used to map the Halpha and [O III] 5007 A emission-line profiles across the entire disk of the edge-on Sb galaxy NGC 4388. We confirm a rich complex of highly ionized gas that extends ~4 kpc above the disk of this galaxy. Low-ionization gas associated with star formation is also present in the disk. Evidence for bar streaming is detected in the disk component and is discussed in a companion paper (Veilleux, Bland-Hawthorn, & Cecil 1999; hereafter VBC). Non-rotational blueshifted velocities of 50 - 250 km/s are measured in the extraplanar gas north-east of the nucleus. The brighter features in this complex tend to have more blueshifted velocities. A redshifted cloud is also detected 2 kpc south-west of the nucleus. The velocity field of the extraplanar gas of NGC 4388 appears to be unaffected by the inferred supersonic (Mach number M ~ 3) motion of this galaxy through the ICM of the Virgo cluster. We argue that this is because the galaxy and the high-|z| gas lie behind a Mach cone with opening angle ~ 80 degrees. The shocked ICM that flows near the galaxy has a velocity of ~ 500 km/s and exerts insufficient ram pressure on the extraplanar gas to perturb its kinematics. We consider several explanations of the velocity field of the extraplanar gas. Velocities, especially blueshifted velocities on the N side of the galaxy, are best explained as a bipolar outflow which is tilted by > 12 degrees from the normal to the disk. The observed offset between the extraplanar gas and the radio structure may be due to buoyancy or refractive bending by density gradients in the halo gas. Velocity substructure in the outflowing gas also suggests an interaction with ambient halo gas.Comment: 29 pages including 5 figures, Latex, requires aaspp4.sty, to appear in ApJ, 520 (July 20, 1999 issue