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AHA2020 – The Next Steps in Treating Heart Failure

AHA 2020 came and went, and now is the time to put into context the scientific advances presented. While all areas of cardiology saw therapeutic innovations, the ever-evolving landscape for heart failure (HF) therapies stood out in particular.

These were among the key discoveries shared at AHA20 in the HF space:

GALACTIC-HF: In patients with chronic heart failure with a reduced ejection fraction (HFrEF), the cardiac-specific myosin activator omecamtiv mecarbil reduced the primary composite endpoint of time to HF event or cardiovascular death, driven by a reduction in hospitalizations and ED visits. Importantly, the therapy appeared to be hemodynamically neutral, and subgroup analysis showed those with lowest ejection fraction (EF) may benefit in particular.

AFFIRM-AHF: In patients with HFrEF and iron deficiency stabilized from an acute HF event, IV iron repletion reduced the risk of subsequent hospitalization for HF but not death.

SOLOIST-WHF: In patients with worsening HF, the SGLT1/2 inhibitor sotagliflozin significantly reduced the risk of death and hospitalization for HF subgroup analysis showed the results persisted regardless of EF.

SCORED: In patients with diabetes and chronic kidney disease, sotagliflozin reduced the risk of cardiovascular death and subsequent hospitalization and/or urgent visits for HF. Similarly, the effect was seen regardless of EF.

These results not only add to the proven therapies for HFrEF including the cornerstones of ARNI, MRA, BB, and SGLT2 inhibitors, they add therapies for worsening heart failure and strongly suggest therapy for heart failure with a preserved ejection fraction. They may even hint at therapy for those with very low EF. With the VICTORIA trial showing benefit for vericiguat at ACC 2020, and additional therapies already indicated for subsets of patients including ivabradine and fixed-dose isosorbide dinitrate and hydralazine, we now find ourselves with a number of medications our patients should be receiving.

The path forward will be deciphering how best to implement these therapies at doses with proven benefit. Dealing with the issue of cost will be key. Sequencing trials, collating datasets with prescription fill data, machine learning tools to support clinical decision making, and personalized medicine through “omics” technologies may all play a role, as recently discussed by the HF Collaboratory (1).

While there is much to be seen, it’s certainly a very exciting time for heart failure!

 

Reference

  1. Bhatt AS, Abraham WT, Lindenfeld J et al. Treatment of HF in an Era of Multiple Therapies: Statement From the HF Collaboratory. JACC: Heart Failure 2020.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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From evidence to practice: Insights from the GWTG-HF Registry on the Applicability of FDA Labeling for Dapagliflozin in Heart Failure with Reduced Ejection Fraction

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors continue to amaze the world of cardiovascular pharmacotherapeutics. Initially developed as anti-diabetic agents, SGLT-2 inhibitors have demonstrated a wide range of benefits across various patient subsets, most notably those with heart failure.

The landmark Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, a phase 3, placebo-controlled trial the results of which were published in November 2019, demonstrated that the SGLT-2 inhibitor dapagliflozin reduced mortality and worsening heart failure events, and improved health-related quality of life among patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence or absence of diabetes.1

Based on these DAPA-HF trial results, in May 2020, dapagliflozin was the first SGLT-2 inhibitor approved by the US Food and Drug Administration (FDA) for HFrEF.2 However, as previous registries have shown, many novel evidence-based therapies are either delayed or not optimally utilized in practice. 3,4 Thus, in order to determine the proportion of eligible candidates for the initiation of dapagliflozin and define potential barriers to therapeutic optimization, an analysis of the American Heart Association (AHA)’s The Get With The Guidelines®–Heart Failure (GWTG-HF) registry was undertaken by Vaduganathan and colleagues. This blog is a summary of the results of this analysis, part of TRANSLATE-HF research platform, the results of which were presented at AHA Scientific Sessions 2020, with simultaneous publication in  JAMA Cardiology.5

The GWTG-HF registry: This a large contemporary hospital-based quality improvement registry including a total of 586,580 patients from 529 sites across the United States.

Population of interest: After exclusion criteria were applied, the primary study cohort for this analysis included 154,714 patients hospitalized with HFrEF at 406 sites between January 2014 – September 2019. As with DAPA-HF, the focus was on chronic HFrEF (≤40%) and treatment eligibility of patients based on discharge parameters during the transition to ambulatory care.

Treatment candidates for Dapagligflozin: The FDA label excluded patients with type 1 diabetes and chronic kidney disease (i.e. estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and dialysis). When this FDA label was applied to patients in the above cohort, 81.1% would be candidates for dapagliflozin, with similar proportions across all study years (range 80.4-81.7%). When analyzed for 355 sites with ≥10 hospitalizations (enrolling 154,522 patients), the median proportion of FDA label candidates was similar, at 81.1%.

Eligibility according to diabetic status: Notably, the proportion of eligible patients for dapagliflozin was higher among those withOUT a history of or new diagnosis of diabetes, as compared with those with type 2 diabetes (85.5% vs. 75.6%).

Reasons for not meeting FDA label: The predominant reason for ineligibility for dapagliflozin in this cohort was an eGFR<30 mL/min/1.73 m2 at discharge; this was more frequent among diabetics (23.9%) than non-diabetics (14.3%). Other reasons were far less frequent: 3.2% were ineligible due to chronic dialysis and only 0.02% due to type 1 diabetes.

Especially in terms of ineligibility for Dapagliflozin reported in this publication, it is important to note that this data analysis was undertaken between April 1st to June 30th, 2020. More compelling data from two other pivotal SGLT-2 trials reported after DAPA-HF are likely to further extend SGLT-2 inhibitor treatment indications to patients with more severe CKD. DAPA CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease6 evaluated patients with albuminuric chronic kidney disease with eGFR down to as low as 25mL/min/1.73 m2 and EMPEROR-Reduced7 evaluated patients with HFrEF with eGFR as low as 20mL/min/1.73 m2.

Differences between DAPA-HF Trial Participants vs. FDA Label Candidates in GWTG-HF: Participants in DAPA-HF were younger, less often women, and less often Black compared with participants in GWTG-HF, underscoring the need for greater representation of older adults, women, racial/ethnic minority groups, and those with multiple comorbidities in clinical trials relative to reference usual care (i.e. registry) populations. GWTG-HF registry participants had lower left ventricular EF and eGFR; however, a history of myocardial infarction and percutaneous coronary intervention) were more prevalent among DAPA-HF participants.  The overall prevalence of diabetes was similar between both cohorts (44.1%  in GWTG-HF registry vs 45% in DAPA-HF population). There was a lower use of evidence-based HF medical therapies among GWTG-HF participants, but higher use of implantable-cardioverter defibrillators. Most other clinical characteristics were qualitatively similar between the two groups

Conclusions & implications: A lag from clinical trial to clinical practice is not uncommon for most novel pharmacotherapeutics. However, data from this large, contemporary US hospitalized HF registry show that 4 out of 5 patients with HFrEF, irrespective of type 2 diabetes status are candidates for initiation of dapagliflozin at hospital discharge, supporting broad generalizability to practice. This represents a potential opportunity for in-hospital implementation of evidence-based medical therapies and treatment optimization of stable chronic HFrEF, pending data on safety and efficacy of SGLT2 inhibitors in acute HF (NCT04363697, NCT04298229, NCT04157751).

References

  1. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
  2. US Food and Drug Administration. FDA approves new treatment for a type of heart failure. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure. Accessed on December 1, 2020.
  3. Greene SJ, Fonarow GC, DeVore AD, et al. Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019;73(19):2365-83.
  4. Greene SJ, Butler J, Albert NM, et al. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018;72(4):351-66.
  5. Vaduganathan M, Greene SJ, Zhang S, et al. Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice: The Get With the Guidelines-Heart Failure (GWTG-HF) Registry. JAMA Cardiol. 2020 Nov 13:e205864. doi: 10.1001/jamacardio.2020.5864
  6. Heerspink HJL, Stefánsson BV, Correa-Rotter R. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396.
  7. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-24. 32865377.

 

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The Sweet Spot in Treatment of Heart Failure With Reduced Ejection Fraction: SGLT2 Inhibitors

I am pleased to have the opportunity to summarize an important recent paper on the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors by Drs. Muthiah Vaduganathan, Gregg Fonarow, and colleagues in JAMA Cardiology,1 that was published simultaneously with AHA20.

Background:

SGLT2 inhibitors are a class of medications that were initially developed for management of diabetes but were serendipitously found to be effective in treating individuals with heart failure. In May 2020, dapagliflozin became the first SGLT2 inhibitor approved by the US Food and Drug Administration (FDA) for use in patients with heart failure with reduced ejection fraction (HFrEF) after the pivotal Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, which showed that dapagliflozin reduced heart failure events and mortality.2 In the EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial, use of another SGLT2 inhibitor, empagliflozin, was also found to reduce risk of cardiovascular death and heart failure hospitalizations.3

Major Question Addressed in the Paper: What proportion of contemporary patients with HFrEF in the US are potentially eligible for initiation of dapagliflozin based on the FDA label?

Approach: The investigators studied patients with HFrEF (EF≤40%) who were in the AHA Get With The Guidelines-Heart Failure (GWTG-HF) registry. They assessed patients admitted between January 2014 to September 2019 at 529 sites (started with 586,580 patients). Patients were excluded if they had any of the following based on the FDA label for dapagliflozin: estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 at discharge, dialysis (either history of chronic dialysis or required dialysis during hospitalization), and/or type 1 diabetes. After excluding patients who met the aforementioned criteria and those who had missing discharge eGFR or vital signs, the primary study cohort consisted of 154,714 patients at 406 sites.

Major Results:

  • Of the 154,714 patients studied in the GWTG-HF registry, 125,497 (81.1%) were candidates for initiation of dapagliflozin based on the FDA label.
  • When only looking at sites with ≥10 hospitalizations (355 sites that enrolled 154,522 patients), the median proportion of dapagliflozin candidates was still 81.1% (25th-75th percentiles 77.8-84.6%).
  • A higher proportion of patients without type 2 diabetes than with type 2 diabetes were candidates for dapagliflozin (85.5% vs. 75.6%).
  • The most frequent reason for not meeting the FDA label was eGFR<30 mL/min/1.73 m2, which was met more frequently in patients with a history of or new diagnosis of diabetes than those without diabetes (23.9% vs. 14.3%).
  • There was lower use of evidence-based heart failure therapies in the GWTG-HF patients compared to patients in the DAPA-HF trial.

Histogram from Vaduganathan et al. evaluating the proportion of patients meeting the dapagliflozin FDA label criteria from hospitals with at least 10 eligible HFrEF hospitalizations.

Major Study Limitations: Since the GWTG-HF data are de-identified, only unique hospitalization episodes were presented so some patients may be represented more than once in this study. Glycated hemoglobin levels were not measured in a protocolized way, thus type 2 diabetes could be underdiagnosed in this study. Data regarding post-discharge labs and the use of therapies were not available.

Key Take Home Message: This study using a large AHA registry (GWTG-HF) strikingly found that 4 out of 5 adults with HFrEF (regardless of whether the patient has type 2 diabetes) may be eligible for initiation of dapagliflozin, supporting the broad applicability of this therapy in US clinical practice.

For further learning, there are several great OnDemand sessions from AHA20 on SGLT2 inhibitors.

AHA20 OnDemand Sessions on SGLT-2 inhibitors:

  • New Glucose-Lowering Agents with CV Benefits: Working… But How?
  • SGLT2i for Non-Diabetic Indications: Updates from Mega-Trials and Mechanistic Insights
  • Novel Anti-Diabetic Agents: A Tidal Wave of Change in the Cardiovascular Care of Patients with CKD
  • The Heart, the Kidney, and SGLT2 Inhibition: For Clinical Trials to Patient Care

Potential Future Research Directions:

  • Determine the mechanisms leading to the efficacy of SGLT2 inhibitors in HFrEF.
  • Investigate the renal effects of SGLT2 inhibitors and whether SGLT2 inhibitors can be safely used in patients with more severe chronic kidney disease.
    • DAPA-CKD4 (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), which included patients with eGFR as low as 25 mL/min/1.73 m2, showed that dapagliflozin reduced risk of sustained eGFR decline of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes regardless of the presence or absence of type 2 diabetes.
    • EMPEROR-Reduced included HFrEF patients with eGFR as low as 20 mL/min/1.73 m2.
  • Evaluate whether SGLT2 inhibitors are beneficial in patients with heart failure with preserved ejection fraction (HFpEF). Current ongoing/future clinical trials with HFpEF patients include DELIVER (NCT03619213), EMPEROR-Preserved (NCT03057951), EMPA-HEART 2 (NCT04461041), PRESERVED-HF (NCT03030235), and EMBRACE-HF (NCT03030222).
  • Assess the effects of simultaneous use of SGLT2 inhibitors and another class of diabetic medications that have shown beneficial cardiovascular disease (CVD) effects, glucagon-like peptide-1 receptor agonists (GLP-1RA) and determine which of these two classes of medications should be prioritized in drug-naïve patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

Potential mechanisms underlying the beneficial effects of SGLT2 inhibitors. Figure from Dr. Subodh Verma’s talk entitled “SGLT2 inhibitors: Why do they work” in the “New Glucose-Lowering Agents with CV Benefits: Working… But How?” session at AHA20.

 

References

  1. Vaduganathan M, Greene SJ, Zhang S, Grau-Sepulveda M, DeVore AD, Butler J, Heidenreich PA, Huang JC, Kittleson MM, Joynt Maddox KE, McDermott JJ, Owens AT, Peterson PN, Solomon SD, Vardeny O, Yancy CW, Fonarow GC. Applicability of us food and drug administration labeling for dapagliflozin to patients with heart failure with reduced ejection fraction in us clinical practice: The get with the guidelines-heart failure (gwtg-hf) registry. JAMA Cardiol. 2020
  2. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM, Investigators D-HTCa. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008
  3. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F, Investigators E-RT. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-1424
  4. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC, Investigators D-CTCa. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-1446

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Highlights from AHA20

AHA20 is wrapping up today with the final sessions. It’s been another excellent meeting with tons of new data that was presented. One consistent theme remains, debates continue to drive the conversation in the management of patients with cardiovascular diseases.

  1. The ISCHEMIA trial did not disappoint again. It led to great discussions regarding the contemporary management of patients with stable ischemic heart disease.”- First, the debate regarding PCI vs optimal medical therapy rages on. Dr. Sripal Bangalore and Dr. William Boden make their case for their approach to managing these patients.

The post ISCHEMIA world left us with burning questions about the optimal approach to imaging.

– CT vs SPECT for the evaluation of patients with SIHD

Guidelines will be surely updated after this landmark trial, but what remains certain is that a patient-centered approach to imaging is the key to optimal decision making.

 

  1. Optimizing GDMT in HF patients with more pills. How much is too much?

This year’s sessions added to our armamentarium in the management of patients with Heart failure and reduced ejection fraction (HFrEF). The GALACTIC-HF trial enrolled 8256 patients with LVEF <35% and pro-BNP >400 pg/ml to receive Omecamtiv Mercabil vs. placebo. With a primary composite outcome of cardiovascular death or CHF event, those enrolled to receive the selective cardiac myosin activator in addition to GDMT demonstrated a reduction in the primary composite outcome, driven by a reduction in CHF events.

The results of this trial brought on questions regarding where newer agents in our HFrEF patients would rank in importance. Do we run the risk of polypharmacy and non-adherence with each newer agent? How much bang for our buck can we expect to receive?

Key takeaways from the discussions regarding GDMT include:

  1. Early initiation and up-titration of medical therapy improve outcomes in HF patients.
  2. Recognize signs of worsening HF and decompensation
  3. Referral to advanced heart failure cardiologists when you need help.

Debates trigger conversations, conservations lead to action. Action in this setting leads to improved patient outcomes. AHA 2020 Scientific Sessions was no different and provided great examples of this rhetoric.

One thing not up for debate at this year’s Scientific Sessions was clear. It was the call to action against structural and institutionalized racism, the fight for diversity, equity, and inclusion for all. From the opening address to the final sessions, AHA 2020 made it a point to bring these conversations to the forefront to impact change. At the end of these 5 days, I feel re-invigorated and optimistic that our actions moving will speak louder than our words. Here’s to hoping we can meet again in person at next year’s Scientific Sessions.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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A new and evolving health struggle for Heart failure patients: COVID-19

It’s safe to say we are not living in normal times.  This is Heart Failure (HF) in the time of the coronavirus disease-2019 (COVID-19). Patients with COVID-19 and preexisting cardiovascular disease (CVD) are at an increased risk of severe disease and death. Moreover, infection has also been associated with cardiac injury such as acute myocardial infarction (AMI), myocarditis, and stress-induced cardiomyopathy leading to subsequent cardiogenic shock (CS) requiring advanced heart failure therapies. There is a bidirectional relationship between viral upper respiratory traction infection(URI) and worsening HF with an increase in hospital re-admission rate as previously noted with influenza. Patients with HF are especially susceptible to influenza-related complications, including acute decompensated HF and secondary pneumonia. Furthermore, HF is associated with greater in-hospital mortality and adverse clinical outcomes. With around 1 million confirmed COVID-19 cases and counting in the US, one would expect an increase in heart failure admissions. Over the past several weeks as the number of COVID-19 admissions increase, the number of patients admitted with heart failure admissions have been at their lowest, which raises the following question: Where are all the HF patients?

We can speculate that people are terrified at home so they are not showing up to the emergency departments. Patients could be slowly accumulating fluids and getting into a decompensated state. On the other hand, being less active, they could also have been experiencing less symptoms. First it was influenza season now overlapping with a COVID-19 pandemic. It would be expected to see an increased number of HF admissions.  It is suggested that we might be experiencing the calm before the storm when it comes to HF decompensation requiring hospitalization. The alternative is that social distancing is the remedy that we have long been waiting for to help decrease heart failure exacerbation and hospital re-admissions rates.

On one bright note, during a telehealth cardiology visit follow up with a long-term patient with chronic systolic heart failure known to have been admitted several times during the past year secondary to medication non-adherence, who admits that he has been feeling great. He takes all his medications religiously now, including his diuretics. He states that the fact that he stays home, he doesn’t have to worry about going to the bathroom to urinate so often when he gets out of the house, therefore he doesn’t miss any of his diuretic doses. He is also compliant with diet as he doesn’t eat out as often as he is used to. He admits that he stopped going out to fast food places. This is one very small sample. On the other hand, on another telehealth visit, there is a patient with newly diagnosed Non-Ischemic Cardiomyopathy and HF with reduced ejection fraction, who is been followed for up-titration of guideline directed medical therapy. It was a challenge to safely increase the dose of his medications without vital signs and avoiding to have the patient physically get to a laboratory to get blood work done. As of now, no major changes were made in the patient current management. Of note, patient did ask about holding angiotensin-converting enzyme (ACE) inhibitors because of what he heard from another source. Once more, no changes were made to the medical regimen and it was explained that it has been recommended based on different society guidelines and expert consensus report, to continue with ACE inhibitors1.

COVID-19 times are dynamic and medical information is constantly being updated. This is an ongoing discussion as the clinical data comes in. As the pandemic evolves and more telehealth visit under our belts, we will continue to find out more. Although as our health care system is currently fighting the COVID-19; we must brace ourselves for the aftermath whether our patients are dying at home, or slowly decompensating. Only time will tell.  As we are flattening to curve with social distancing, our patients with chronic conditions like HF are waiting at home with so much uncertainties surrounding their current and future medical care. “When life gives you lemon, make lemonade”.

The following suggestions can be useful when taking care of heart failure patients during these unprecedented times. (Figure 1) With COVID-19, we should let our HF patients know although social distancing is essential, they are a higher risk population for a complicated course if infected. It is important to inform them on when to seek medical care, whether it’s to contact a health care provider, call emergency medical services, or go to the emergency department. Although, prevention remains the best medicine. They should take the extra step in precautions and follow the latest recommendations from their local department of public health as we should always remind them of what those recommendations consist of via our telehealth visits.  From a cardiologist stand point, it is important to remain available whether it is via email, pager and/or more frequent telehealth visit if possible.  If they don’t have a scale and/or automatic blood pressure machines, it should be suggested to obtain them along with a thermometer from their local pharmacies. With a phone camera, it is feasible to assess Jugular Venous Distention, pitting edema. In addition, with weight trends, blood pressure and heart rate, clinical decisions could be made.  If available, assessment of data via CardioMEMS can also be very helpful in making medical decisions. Desperate times call for desperate measures.  This is too shall pass. If this is the calm before the storm for our heart failure patients, we should be ready when it hits remembering the sun always shines after a storm.

Figure 1. Heart Failure Care Suggestions During COVID-19

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

 

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Another (Louder) Call to Improve the Care We Provide Heart Failure Patients

I am always taken aback when I recommend a switch to sacubitril/valsartan in a patient with heart failure with reduced ejection fraction (HFrEF) and the response is “my patient feels fine”. This is a common response and certainly not a good enough reason to not optimize guideline directed medical therapy (GDMT) in patients with HFrEF. Optimization of GDMT in HFrEF, known to improve morbidity and mortality (1,2), is dismal. The Change the Management of Patients with Heart Failure (CHAMP-HF) registry included patients in the United States with chronic HFrEF receiving at least one oral medication for management of HF and showed >25% of eligible patients are not prescribed angiotensin converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor, >33% are not prescribed a beta blocker, >50% are not prescribed a mineralocorticoid receptor antagonist. Remarkably, even among those receiving GDMT fewer than 25% are prescribed target doses and only 1% of eligible patients are simultaneously on target doses of all 3 classes of GDMT (3,4).

The mechanisms for suboptimal prescription of GDMT in HFrEF are complex and undertreatment is even more evident among women, minority patient populations, and patients from economically disadvantaged backgrounds, among others. Cost is certainly an issue, especially with more novel HF therapies and co-pay assistance programs are not always available to our most vulnerable patients. There are not enough HF cardiologists to take care of the continuously increasing population of HF patients and therefore, optimization of GDMT needs to be done by general cardiologists and primary care clinicians as well. We should also become creative and use telemedicine to optimize GDMT more efficiently. We do our patients a disservice by not optimizing GDMT that improves HF morbidity and mortality.

And just as optimization of GDMT is not ideal, neither is our evaluation of etiology of HF. Optimization of GDMT and determination of etiology of HF whose management may change disease trajectory should be undertaken in all patients with new-onset HF. This begins with a fundamental understanding of the various etiologies of HF, the laboratory and imaging testing needed, and the best treatment strategy for the underlying etiology discovered- if any (cue, “idiopathic” cardiomyopathy). O’Connor and colleagues’ observational cohort study from the Get With The Guidelines- Heart Failure (GWTG-HF) registry demonstrates the need to improve the testing we perform to exclude coronary artery disease (CAD) as the underlying etiology of new-onset HF.4

Why is this important? Well, of course for treatment, which involves deciding whether medical therapy (aspirin, statins) or revascularization (surgical or percutaneous) is a more optimal strategy. And most important to improve disease trajectory as continued ischemia will lead to worsening HF. O’Connor and colleagues found that the majority of  17,185 patients hospitalized for new-onset HF did not receive testing for CAD either during the hospitalization or in the 90 days before and after, despite data demonstrating that 60% (!!!) of HF patients have concomitant significant CAD.4 And consistent with disparities I mentioned earlier regarding the undertreatment of women with GDMT, men were more likely to be tested for CAD.

Diagnosing and treating CAD provides an opportunity to discuss risk factor modification with patients such as smoking cessation, diabetes control, exercise, healthy diets etc.… to further mitigate future risk. The importance of optimization of GDMT in patients with HFrEF cannot be understated and analogous to this, is the importance of examining the underlying etiology of HF in patients with new-onset HF with preserved, borderline, or reduced EF to improve disease trajectory. Furthermore, inequities in both aspects of the care of HF patients in terms of identification of etiology and optimization of GDMT, must be addressed on a national level. We have plenty of data illustrating suboptimal optimization of GDMT in those with established HFrEF and suboptimal testing for CAD in those with new-onset HF. The next steps are understanding the mechanisms and implementing strategies to improve care. The need for this is critical to reduce morbidity and mortality in all HF patients.

References

  1. Yancy CW, Jessup M, Bozkurt B et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017;137.
  2. Yancy CW, Januzzi JL, Allen LA et al. 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction. Journal of the American College of Cardiology 2017.
  3. Greene SJ, Butler J, Albert NM et al. Contemporary Utilization and Dosing of Guideline-Directed Medical Therapy for Heart Failure with Reduced Ejection Fraction: From the CHAMP-HF Registry. Journal of the American College of Cardiology 2018.
  4. O’Connor, Kyle D., et al. “Testing for Coronary Artery Disease in Older Patients With New-Onset Heart Failure.” Circulation: Heart Failure, vol. 13, no. 4, 2020, doi:10.1161/circheartfailure.120.006963.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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COVID-19; Patients with Congenital Heart Disease (CHD)

This week, the ACHA (American Congenital Heart Association) hosted a webinar in regards to Coronavirus aka SARS-CoV-2, and the illness it causes, COVID-19, 3,000 attended (view the recording here.) CHD patients, parents of CHD patients and CHD providers had the same question, how does this virus affect this special population? Unfortunately, the data is lacking on coronavirus those with CHD and there is a lot we don’t know.

A recent study1 in China looked at 2143 pediatric patients with COVID-19, the majority (94.1%) were asymptomatic or mild, more severe cases, were seen in infants (<1 year old) than older children, and there was only one death. This study lacks details, such as what other medical conditions they may have. Severe cases were 5.9% compared to 18.5% in adult population studies. Although reassuring for the general pediatric population, we still don’t know how this applies to pediatric patients in the United States and those with CHD.

What we do know.

There is a trend toward overgeneralization of “heart disease,” particularly in the media. It has been noted that the COVID-19 affects older adults and those with “heart disease,” meaning cardiovascular disease(CVD), such as coronary artery disease and hypertension, more severely.2 This does not include Congenital Heart Disease.

The virus may also cause myocardial injury, with reports of myocarditis and arrhythmias in those with severe cases.2-4 The effect is thought to be related to Angiotensin-converting enzyme 2(ACE2), which, in animal studies, has a role in the cardiovascular, and immune system and has been identified as a functional receptor for coronaviruses.2,3

Many patients with CVD and CHD take a medication known as ACE inhibitors or an Angiotensin Receptor Blockers (ARBs). The use of these medications is common in both populations, but for different indications, as their “heart disease” is not the same. There are trials assessing the use of these medications and effect on COVID19 in adults, and varying theories on whether they are protective or not, with that said, the HFSA/ACC/AHA currently recommends continuing these medications as prescribed.5

Are patients with CHD considered high risk?

The answer is we don’t know. With a wide range of congenital heart disease, from repaired/“normal” hearts, to those with altered blood flow, lung abnormalities, and arrhythmias. As  mentioned, the CDC places those with “heart disease,” meaning those with CVD, and older adults, at high risk of severe illness,6 this does not include CHD, however, CHD patients aren’t immune to CVD and if a patient has CVD and also CHD they are considered high risk.

With data lacking in many populations, it is important for those considered at high risk for other viruses, like influenza, such as CHD, asthma and those who are immunocompromised, to take appropriate precautions. It is better to be over prepared and over cautious.

Follow up and Communication.

CHD patients should keep in close contact with their medical team and stay updated with recommendations of their team and the CDC (found in detail here), like social distancing, good hand hygiene and staying home if you are sick. Concerning symptoms that require further evaluation include shortness of breath (or fast breathing in infants), chest pain, and palpitations.

 As far as visiting your doctor, you will likely be asked to either re-schedule or have a telephone visit. You can ask your medical team about this option and even anticipate it for the next few months. Elective procedures, catheterizations and imaging will likely be delayed. If one good thing comes out of this pandemic, it may be better options and availability for telemedicine in the future.

Keep your Mind Healthy

Use this time to support your mental health— pay attention to the news and social media, but set timers so you don’t over-saturate yourself. Find the book you’ve had on your shelves that you’ve been too busy for and set aside time every day to read, call or FaceTime friends, and maybe even fill up your bathtub and relax!

Meditation and exercise are also great options, and many apps offer free trials. Calm and Headspace have some free mediation content and free trials. Peloton & DailyBurn offer free day trials with a variety of classes(Tip: If you do choose a free trial, be sure to set an alarm on your calendar before the free trial is over so you can choose if it’s worth continuing for a fee or not.) There are also options to support your local gyms and studies virtually with on demand classes, just check out their websites and/or Instagram.

There is so much unknown, which causes us to worry and discomfort, but we are learning more each day. Stay informed, stay safe, wash your hands and try to keep your mental health in check.

For more on coronavirus and heart health, read Noora Aljerhi’s blog (3/9/2020) on the early career voice.

  1. Dong, Yuanyuan, et al. “Epidemiological Characteristics of 2143 Pediatric Patients with 2019 Coronavirus Disease in China.” Pediatrics, 2020, doi:10.1542/peds.2020-0702.
  2. Hui, Hui, et al. “Clinical and Radiographic Features of Cardiac Injury in Patients with 2019 Novel Coronavirus Pneumonia.” 2020, doi:10.1101/2020.02.24.20027052.
  3. Zheng, Ying-Ying, et al. “COVID-19 and the Cardiovascular System.” Nature News, Nature Publishing Group, 5 Mar. 2020, nature.com/articles/s41569-020-0360-5?code=85e25438-46d1-4753-bfdd-84496a98b564.
  4. Hu, Hongde, et al. “Coronavirus Fulminant Myocarditis Saved with Glucocorticoid and Human Immunoglobulin.” European Heart Journal, 2020, doi:10.1093/eurheartj/ehaa190.HFS/ACC/AHA statement
  5. “HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19.” American College of Cardiology, 17 Mar. 2020, acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19.
  6. “If You Are at Higher Risk.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 12 Mar. 2020, www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Heart Failure Management and the Challenge of Systems-Based Practice Implementation for Optimization of Guideline Directed Medical Therapy

As the population continues to age, along with the addition of lifesaving and prolonging medical therapies, the prevalence of HF will continue to increase. In this article, we will solely focus on Heart Failure with Reduced Ejection Fraction (HFrEF), and the potential solutions to the issues with the optimization of guideline directed medical therapy (GDMT) on a systems level.

Robust evidence has established a mortality benefit of GDMT for patients with left ventricular dysfunction. Although the known benefits of GDMT have continued to solidify, there remains a visible gap among patients with HFrEF and the efficacy of treatment.

The issues that exist are likely not based on the individual pharmaceutical therapies profile. Furthermore, medication intolerance and incomplete prescription data can only partially be blamed. Nevertheless, the problems are on a bigger scale, and they involve many different components of our care system.

Let’s discuss some of the barriers to the optimization of GDMT in patients with HFrEF: patient providers and the care system. Providers, including non-cardiologists, should be trained adequately to be able to initiate patients on appropriate medications for HFrEF. They should also know the threshold to discontinue the medications, their side effects, the major contraindications, and, most importantly, when to seek help. HF patients are often complex, and it is essential to know that the different providers involved in their care should be in constant communication when it comes to their medical regimen. It is not enough to start the medication. It’s of utmost importance to continue increasing the dosages as tolerated by the patient to at least the dosages used in the different studies where these medications have shown the most benefits. Education is a key aspect, and it should involve the patient, patient’s family, providers, and everybody in the care system responsible for the patient including nurses and pharmacists. I propose 2 points among many out there:

  1. Standardized education for everybody involved in the patient’s care
  2. Standardized methods of communication between the different providers involved in the patient’s care including the patient and their families.
Heart Failure Summit 2017 Overview: Improving care and outcomes in heart failure

Figure 1. Heart Failure Summit 2017 Overview: Improving care and outcomes in heart failure1.

The purpose of this article is not to re-invent the wheel. The American Heart Association Heart Failure Summit in 2017 identified opportunities to improve care and outcomes and reduce disparities for patients with HF.(Figure 1). The purpose of this article is to remind us that we should be focusing more on implementation strategies for GDMT. We already have the tools, and, as we speak, we are adding new ones. It’s not just the tools; it is how you make use of them that will be the difference.

In summary, establishing and implementing systems of care that can help increase the number of patients on GDMT with the focus on improving medication adherence will ultimately lead to better outcomes. What is certain is that we must continue to meet the challenges of the realities of GDMT and their barriers. Our patients with heart failure depend on it.

References

  1. Pamela N. Peterson. Circulation: Heart Failure. The American Heart Association Heart Failure Summit, Bethesda, April 12, 2017, Volume: 11, Issue: 10, DOI: (10.1161/CIRCHEARTFAILURE.118.004957)

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.

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How My Heart Failure/Transplant Fellowship Changed Me

When I started my Advanced Heart Failure/Transplant fellowship, my program director told me this year would change my life. I thought, “Yeah okay, whatever.” Boy, did that year change my life. The way I looked at the world changed entirely. Transplant is one of the most incredible medical therapies available to patients with end-stage heart, kidney, and liver disease, amongst others. Because of the generosity of the donor and the donor’s family, someone else is given a second chance at life. I always tell my heart transplant patients that they should now be celebrating 2 birthdays every year- to commemorate the gift of life given to them a second time over.

When I say that year changed my life, it truly did, and that change is lasting. When we’re on heart donor call and we’re evaluating hearts for suitability for our recipients, they’re usually younger hearts and cause of death is almost always unexpected. The stories are tragic- suicides, car accidents, freak accidents, and unintended drug overdoses, amongst other causes of death. As I sit in my pajamas (donor heart evaluations happen in the middle of the night a lot) on my laptop making sure I look through all personal and medical details available to me, I can’t help but create an image in my mind of who this donor is, what they may have looked like, where they worked, how much pain they must have been in if their death was intentional, and most gut-wrenching is all the people they left behind. Death is never easy, but when the donors are young, when the deaths are intentional, when the deaths are completely unexpected, it makes me realize how grateful we should be for this life we are living.

That year completely changed how I look at the world. No longer was I going to “sweat the small stuff” whether they were work related or personal. Every donor call reminds me that we sometimes spend so much time, energy, and emotions on things that, in the grand scheme of life, are truly insignificant. I became a happier and more content person. This year taught me that human connections are the most important thing in this world. My family, the friends I consider family, my friends at work, my patients, and all the people I cross paths with that have an impact on my life.

And on the other side of death, after I have pictured this life lost and the family and friends they’ve left behind, I get to tell one of our patients with end-stage heart failure that a heart “has become available” to them and now their life is going to change. I can’t imagine how they feel but I’ve heard all kinds of the emotions on the other end of that phone- tears, shock, anxious smiles that can be heard through the phone, and more tears. My patients tell me it’s a very emotional experience from the time they’re listing. Some have said it feels weird to be “waiting for someone to die” so that they can live. Some have noted guilt. Some of my patients have developed relationships with their donor’s families and I can only imagine how surreal that must feel.

What I do know is that I couldn’t imagine myself doing anything else and that being a Transplant Cardiologist has truly changed my life. I am grateful to the patients who have allowed me to play a small role in their journey and forever grateful to the donors and their families for this incredible gift of life.

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Thiamine: An Important Nutrient to Consider in Treatment of Congestive Heart Failure

Thiamine deficiency is an uncommon nutritional deficiency in the developed world. The population most at risk in North America and Europe has been noted to be alcoholics with poor diets. This nutrient deficiency can manifest as several different syndromes, one of which is “beriberi.” Beriberi was first described by Dr. Wenckebach in the early 1900s who observed the presence of dependent edema, elevated venous pressures, and an enlarged heart in patients who had three or more months of a thiamine deficient diet, with recovery after thiamine administration. What followed years after were several case reports of alcoholics with signs of congestive heart failure who improved drastically with administration of thiamine.

Although today beriberi heart disease is a rare diagnosis, what it does show is that thiamine is an important micronutrient for the heart, and lack of thiamine can cause symptoms of heart failure.

Given that thiamine is excreted through the urine, another population that has been deemed to be at risk for thiamine deficiency is those on high doses of diuretics such as furosemide1. Interestingly, this population includes the difficult-to-control heart failure patients that we see on the wards every day. Biochemically, one study has shown that thiamine uptake in cardiac cells can be inhibited by furosemide2.

Yet, treatment of patients with congestive heart failure on diuretics with thiamine is not currently standard of practice.

Looking at the literature, there have been only two randomized double blind placebo controlled trials on thiamine use in patients with congestive heart failure: Shimon et al 19953 and Schoenenberger et al 20124. Both of these trials showed a statistically significant increase in left ventricular ejection fraction with the use of thiamine in patients presenting with symptomatic congestive heart failure. Granted, the ejection fraction only improved by 3-4% which we could say was due to echocardiography interpretation variability. However, being that thiamine is cheap and there is evidence that points towards its use as a medication in heart failure, should we institute it into our daily practice?

What do you think?

 

References:

  1. Katta N, Balla S, Alpert MA. Does Long-Term Furosemide Therapy Cause Thiamine Deficiency in Patients with Heart Failure? A Focused Review. Am J Med. 2016;129(7):753.e7-753.e11.
  2. Zangen A, Botzer D, Zangen R, Shainberg A. Furosemide and digoxin inhibit thiamine uptake in cardiac cells. Eur J Pharmacol. 1998;361(1):151-5.
  3. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98(5):485-90.
  4. Schoenenberger AW, Schoenenberger-berzins R, Der maur CA, Suter PM, Vergopoulos A, Erne P. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. Clin Res Cardiol. 2012;101(3):159-64.