Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a Preliminary Study on Heart Failure with preserved Ejection Fraction
Article Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 5/11/2022
For heart failure patients with mildly reduced or preserved ejection fraction in the DELIVER trial, dapagliflozin (Farxiga) helped reduce the risk of cardiovascular death and worsening heart failure, AstraZeneca announced, paving the way for a new indication in the future.
But how many real-world heart failure patients would actually be eligible for SGLT2 inhibitors based on trial criteria? (Journal of Cardiac Failure)
SOURCE
UPDATED on 8/28/2021
Empagliflozin in Heart Failure with a Preserved Ejection Fraction
List of authors.
Abstract
BACKGROUND
Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
METHODS
In this double-blind trial, we randomly assigned 5988 patients with class II–IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.
RESULTS
Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin.
CONCLUSIONS
Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951. opens in new tab).
UPDATED on 2/12/2019
Prescription of Potentially Harmful Drugs in Young Adults With Heart Failure and Reduced Ejection Fraction
Correspondence information about the author MD Paulino A. Alvarez
Email the author MD Paulino A. AlvarezEmail the author MD Paulino A. Alvarez,
,
,
The Voice of Dr. Justin D. Pearlman
The selection of medications for patients with multiple conditions (co-morbidities) always raises conflicts. This is true in general, and especially true for patients with heart failure.
For example, patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial fibrillation, whereby sustained rapid ventricular response may worsen the failure due to tachycardiomyopathy. In essence, sustained high heatrates deplete supplies and weaken the heart, which can take months of controlled rates to recover.
Medications to control the rate are problematic. Digoxin increases the death rate. Beta blockers and diltiazem decrease the heartrate but also decrease contractility (EF), and in combination may stop the heart (complete heart clock, cardiac arrest). Anti-arrhythmic agents also decrease contractility. Use of beta blockers is encouraged because benefits often outweigh the harm, though in some cases the decline in contractility results in unacceptably low blood pressure. Some patients with rate control issues do not tolerate beta blockers but do better on diltiazem instead. Thus the list of medications that may worsen heart failure constitute “relative contraindications” which means concerning but still possibly useful.
In other words, some of the medications that may worsen ejection fraction have net benefit, and may be used with caution.
Non-steroidal anti inflammatory agents (NSAIDs) are another example. They relieve pain and add function to patients limited by arthritis. High dose ibuprofen tapered over one month can stop pericarditis, as an alternative to colchicine which may be limited by causing intractable diarrhea. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease prostaglandin synthesis and, thus, may precipitate fluid retention in patients with heart failure. They also increase blood pressure, impair renal function and promote thrombosis (clotting). Use of NSAIDS has not been shown to curtail joint damage to joints, and daily use for 18 months or more promotes coronary disease. Overall, NSAIDs appear to be over utilized.
The high incidence of use of medications that may cause or worsen reduced EF heart failure is a concern of caution. Such use merits continual monitoring for net harm versus benefit on an individual basis. The study in AJC documenting the high incidence of use of medications that worsen heart failure in patients already known to have reduced ejection fraction is helpful as a reminder of caution highlighting the importance of individualizing medication choices, but should not be rigidly interpreted as absolute contraindication or presumed error.
SOURCE
From: Justin MDMEPhD <jdpmdphd@gmail.com>
Date: Tuesday, February 12, 2019 at 7:53 AM
To: Aviva Lev-Ari <aviva.lev-ari@comcast.net>
Subject: Re: Almost 25% of HFrEF patients prescribed drugs that could worsen their condition
UPDATED on 1/15/2019
Andrew Perry, MD, interviews John Gorcsan III, MD
In this episode, Andrew Perry, MD, discusses the utility of ejection fraction (EF) with John Gorcsan III, MD, an expert in echocardiography and strain imaging at Washington University School of Medicine in St. Louis.
They explore how EF came to be used in clinical practice, the importance of it in heart failure and the variation in measurement. The interview also covers strain imaging and what it adds to ejection fraction, particularly in the setting of severe mitral regurgitation.
UPDATED on 1/9/2019
HFrEF: NT-proBNP decrease marks reverse remodeling, better outcomes
Source: JACC Heart FailCurated by: Jenny Blair, MDJanuary 08, 2019Takeaway
- In heart failure (HF) with reduced ejection fraction (HFrEF), a drop in pro-B-type natriuretic peptide (NT-proBNP) to <1000 mg/mL reflects reverse remodeling and improved ejection fraction (EF).
- Authors suggest that response to treatment based on change in NT-proBNP might outweigh treatment strategy.
Why this matters
- Whether lower NT-proBNP levels reflect changes in cardiac structure and function has been unclear.
Key results
- 12-month changes with guided therapy vs without:
- No significant between-group differences in left ventricular (LV) end-systolic volume index (ESVi), NT-proBNP, EF.
- Changes among subgroup whose NT-proBNP fell to <1000 pg/mL (n=52):
- ESVi and end-diastolic volume index (EDVi) reductions: 17.3 and 15.7 mL/m2, respectively;
- EF: 9.9%±8.8% vs 2.9%±7.9% in nontarget achievers (P<.001);
- Death or HF hospitalization: 0% vs 30% in nontarget achievers (P<.001);
- Greater improvement in global longitudinal strain, less mitral regurgitation.
- Greater reduction in NT-proBNP correlated with significantly greater EF, ESVi, EDVi improvements.
Study design
- Randomized parallel-group multicenter GUIDE-IT Echo Substudy.
- 268 adults with HFrEF, EF ≤40%, NT-proBNP >2000 pg/mL randomly assigned to NT-proBNP-guided therapy vs usual care.
- Outcome: 12-month change in LV ESVi on echocardiography.
- Funding: Roche Diagnostics.
Limitations
- Duration of NT-proBNP <1000 not assessed.
SOURCE
Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC
Pearls From: Ted Feldman, MD – A glimmer of hope for HFpEF treatment?
Evanston Hospital in Illinois
by Contributing Writer, MedPage Today
SOURCE ARTICLE
https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09
WATCH VIDEO
https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09
Heart Failure with preserved Ejection Fraction (or HFpEF) – Experimental Therapy: Inter-atrial shunt implantable device for relieving pressure overload and improve the prognosis of patients with a 50% ejection fraction
vs
Heart Failure with reduced Ejection Fraction (HFrEF)
- HFpEF is similar in frequency and sadly, similar in prognosis to heart failure with reduced ejection fraction, and everybody thinks about the EF 20% or 30% patient as having a poor prognosis and doesn’t realize that the EF 40% or 45% or 50% patient with clinical heart failure has the same prognosis.
- Patients with mitral stenosis and elevated left atrial pressure, which is the genesis of HFpEF, if they had an ASD historically, this decompressed the left atrium and they presented much, much later in the course of the disease with any signs of heart failure.
- Inspiration for design of the Left inter-atrial shunt implant device
Minimally invasive transcatheter closure is the primary treatment option for secundum atrial septal defects (ASD). The AMPLATZER™ Septal Occluder is the proven standard of care in transcatheter ASD closure
- Left inter-atrial shunt implant device, Dr. Ted Feldman calls IASD.
It’s like an ASD occluder, a little nitinol disc, but it has a hole in the middle. We did some baseline hemodynamic modeling using a simulator and calculated that we would get a small shunt with an eight millimeter opening, that that would be enough to reduce left atrial pressure overload during exercise without overloading the right side of the heart, without creating too big a shunt.
Preliminary results: We found that peak exercise wedge pressure was significantly decreased in the patients with the device compared to those without a shunt. We found that the shunt ratio, the amount of flow across the shunt was a Qp:Qs, pulmonary to systemic flow ratio, of 1.2 preserved at 30 days and 6 months and that most of these patients feel better.
Ted Feldman, MD, Evanston Hospital in Illinois
The mechanism, I think we’ve established, that we do decompress the left atrium with exertion and now we need to demonstrate that the clinical outcomes in a larger population are robust enough to carry this into practice.
Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC
- The assertion of “no treatment for HFpEF” (elevated left ventricular diastolic filling pressure) does not give credit to evidence and support for benefit from triple therapy of beta blocker, acei/arb/arni, and aldosterone inhibitor, plus tight blood pressure control and additional afterload reduction if valve leaks contribute to the elevated diastolic filling pressures.
- It is an interesting proposition to induce an 8 mm intra-atrial septum (IAS) shunt, which may indeed unload high pressure in the left atrium and hence unload the left ventricle during diastole (when the mitral valve is open so the left ventricle and left atrium equalize pressures) if patients are very carefully selected and do not have high pressures in the right atrium.
- However, elevated left ventricular pressure is associated with reduced compliance (stiffness) of the left ventricle, for example due to high blood pressure, muscle hypertrophy and fibrosis. Adverse consequences include not only the high pressure which can back up to the lungs, making them boggy and therefore impair oxygen uptake resulting in shortness of breath worse laying down whereby more lung area is affected. The “back pressure” also promotes hepatic congestion and leg swelling. Each of those features of “diastolic failure” which underlies “HFpEF” may benefit from the proposed shunt if right atrial pressures are low, with or without preserved ejection fraction (pEF). However, there is an additional adverse consequence of a stiff left ventricle called “filling dependence” – if pressure is relieved, the left ventricle may under fill, reducing stroke volume and blood pressure, cardiac output (stroke volume times heart rate), thereby reducing organ perfusion. Low blood pressure with lightheaded spells is a common consequence. Over time, metarterioles to the brain can adjust to accommodate lower pressures. The kidneys as well as the brain are very sensitive to adequacy of cardiac output. A marked decline in renal function due to “pre-renal azotemia” is a common consequence that can limit any approach at lowering the diastolic filling pressure, which is seen commonly with use of diuretics to lower pressures.
- The small opening is intended to allow pressure unloading without clots crossing over, but may still pose a risk for paradoxical emboli, which have been associated with
- visual field cuts,
- TIA and
- migraine headaches
Paradoxical Embolism
- Author: Igor A Laskowski, MD; Chief Editor: Vincent Lopez Rowe, MD more…
The clinical manifestations of paradoxical embolism (PDE) are nonspecific, [1] and the diagnosis is difficult to establish. Patients with PDE may present with neurologic abnormalities or features suggesting arterial embolism. The disease starts with the formation of emboli within the venous system, which traverse a patent foramen ovale (PFO) and enter the systemic circulation. [2, 3, 4] PFOs have been found on autopsy in up to 35% of the healthy population.
PDE originates in the veins of the lower extremities and occasionally in the pelvic veins. Emboli may be of various types, such as clots, air, tumor, fat, and amniotic fluid. [5] Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet).
Management of PDE is both medical and surgical in nature. PDE is considered the major cause of cerebral ischemic events in young patients. On rare occasions, it may occlude the pelvic aortic bifurcation. The largest documented thrombus in a PFO (impending PDE) was 25 cm in length.
PDE is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. It may be presumed in the presence of arterial embolism with no evidence of left-side circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO. [6]
SOURCE for Paradoxical Embolism
https://emedicine.medscape.com/article/460607-overview
SOURCE for Dr. Pearlman’s Expert Opinion
From: Justin MDMEPhD <jdpmdphd@gmail.com>
Date: Wednesday, May 9, 2018 at 2:25 PM
To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>
Cc: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>
Subject: Re: WHICH of our Heart Failure ARTICLES I should UPDATE with the following Pearls From: Ted Feldman, MD | Medpage Today
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aptubman
Arav Gandhi
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
zraviv06
zs22
[…] Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a… […]