volume 53, issue 10 october 2021 - audio-digest.org

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Volume 53, Issue 10 October 2021

Editor in ChiefAlison L. Bailey, MD, FACC, FAACVPR

Associate EditorsDhanunjaya “DJ” Lakkireddy, MBBS, FACC Andrew Kates, MD, FACC Clyde W. Yancy, MD, FACC Christopher M. Kramer, MD, FACC Deepak L. Bhatt, MD, FACC C. Noel Bairey Merz, MD, FACC

InterviewersMirvat Alasnag, MB, BCH, FACC Alison L. Bailey, MD, FACC Jeroen J. Bax, PhD, MD, FACC A. John Camm, MD, FACC Richard A. Chazal, MD, MACCAnthony N. DeMaria, MD, MACC James C. Fang, MD, FACC Cindy L. Grines, MD, FACC, MSCAI John Gorcsan III, MD, FACC Christopher B. Granger, MD, FACC Dipti Itchhaporia, MD, FACC Matthew Martinez, MD, FACC Roxana Mehran, MD, FACC Sean P. Pinney, MD, FACC Sidney C. Smith Jr., MD, MACCAllen J. Taylor, MD, FACC Annabelle S. Volgman, MD, FACC

Editors in Chief EmeritusSpencer B. King III, MD, MACC Alfred A. Bove, MD, PhD, MACC (deceased) C. Richard Conti, MD, MACC

Educational ObjectivesThe goals of this activity are to improve the prevention and diagnosis of cardiovascular disease, as well as to improve outcomes of cardiovascular treatments and therapies. After completing the activity, the clinician will be better able to: 1. Provide recently proposed universal definitions of heart failure and myocardial

infarction. 2. Prevent cardiomyopathy in patients with arrhythmia or patients undergoing

treatment of breast cancer. 3. Optimize management of patients with right ventricular failure and pulmonary

hypertension. 4. Explain mechanisms of left and right ventricular dysfunction in patients with

COVID-19 infection.ACCEL is cosponsored by the American College of Cardiology Foundation and Audio Digest. Accreditation: The Lippincott Continuing Medical Education Institute is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.Designation: The Lippincott Continuing Medical Education Institute designates this educational activity for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 4.0 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Lippincott Professional Development is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation. Lippincott Professional Development designates each ACCEL program for 4.0 CE contact hours.Audio Digest is approved as a provider of nurse practitioner continuing education by the American Academy of Nurse Practitioners (AANP Approved Provider number 030904). Audio Digest designates each ACCEL program for 4.0 CE contact hours.The California State Board of Registered Nursing (CA BRN) accepts courses provided for AMA PRA Category 1 Credit™ as meeting the continuing education requirements for license renewal. Provider (Lippincott Professional Development) is approved by the California Board of Registered Nursing, Provider Number CEP 11749.Other healthcare professionals who participate in this activity may submit their CME certificates, if accepted, to their respective boards and accrediting organizations if they are able to utilize AMA PRA Category 1 Credit™. Expiration: This CME activity qualifies for AMA PRA Category 1 Credit™ for 35 months from its date of publication.Estimated time to complete this educational activity:Review Educational Objectives and Faculty Disclosure 5 minTake pretest 10 minListen to audio 3 hrReview complete written summary 35 minTake posttest 10 minNote: Pretest questions are on the last page of this PDF, and on page 4 of the printed summary. ACCEL pretests and posttests can be completed online.

Faculty DisclosureIn adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the planning committee reported nothing to disclose. See pages 2 to 3 for specific disclosures for each interview session included in this program. To view the full list of the ACCEL Editorial Board members’ conflicts of interest, visit: http://legacy .audio-digest.org/pdffiles/ACCEL-disclosures.pdf.

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Volume 53, Issue 10 ACCEL October 2021

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DISC 1

1 Universal Definition of Heart Failure Syndrome: Evolving Strategies

Biykem Bozkurt, MD, PhD, FACC, Houston, TXConsultant Fees/Honoraria: Amgen Inc., Baxter Healthcare, Bristol

Myers Squibb/E.R. Squibb & Sons, Vifor Pharma, Sanofi-Aventis, scPharmaceuticals; Data Safety Monitoring Board: LivaNova USA; Other: Abbott Laboratories, Respicardia

Allen J. Taylor, MD, FACC, Washington, DCSpeaker’s Bureau: Amgen Inc.Correspondent: Michelle D. Kelsey, MD, Durham, NCTake-home Messages:

✹✹ Despite improvements in guidelines and expansion of evidence for life-saving therapies for heart failure (HF), standard therapies (eg, angiotensin-converting enzyme [ACE] inhibitors, β-blockers) continue to be underutilized — demonstrating a lack of standardization in HF care. ✹✹ A textbook definition of HF usually defines HF as the heart’s inability to meet the body’s metabolic demands at the tissue level (which usually applies to advanced, end-stage HF patients). ✹✹ Practice guidelines use varying terminology and parameters to define HF, ranging from signs and symptoms, reduced cardiac output and/or elevated filling pressures, neurohormonal features, and biomarkers. ✹✹ Inconsistencies across guidelines and unclear terminology (about, eg, HF staging nomenclature) create confusion among clinicians as well as patients. ✹✹ The Universal Definition and Classification of Heart Failure is a consensus statement developed by the Heart Failure Society of America, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, and is endorsed by a number of other societies.✹✹ The consensus statement defines HF as a clinical syndrome with current or prior symptoms and/or signs caused by a structural and/or functional cardiac abnormality, and corroborated by elevated natriuretic peptide levels and/or objective evidence of cardiogenic pulmonary or systemic congestion by a diagnostic modality (eg, imaging study).✹✹ The document proposes revised stages of HF. At-risk for HF (former Stage A) — for patients at risk for HF without current or prior symptoms and/or signs and without structural, biomarker, or genetic markers of disease. Pre-HF (former Stage B) — for patients without current or prior symptoms and/or signs, but with evidence of structural heart disease, abnormal cardiac function, or

elevated natriuretic peptide or cardiac troponin levels. HF (former stage C) — for patients with current or prior symptoms and/or signs of HF caused by a structural or functional cardiac abnormality. Advanced HF (former stage D) — for patients with severe symptoms and/or signs of HF. ✹✹ The document also proposes revised classification of HF according to left ventricular ejection fraction (LVEF). HF with reduced ejection fraction (HFrEF) — HF with an LVEF of ≤40%. HF with mildly reduced EF — HF with an LVEF of 41% to 49%. HF with preserved EF — HF with an LVEF of ≥50%. HF with improved EF — HF with a baseline EF of ≤40% with a ≥10-point increase from baseline LVEF, and a subsequent measurement of LVEF >40%.✹✹ The consensus statement specifies terminology for clinical trajectories. For example, use of the term “persistent HF” is preferred over “stable HF,” and “HF in remission” is preferred over “recovered HF.”✹✹ A consensus on HF across different specialties and practitioners will support early and clear detection of HF and an improved understanding of treatment strategies (eg, sodium-glucose cotransporter-2 inhibitors, mineralocorticoid receptor antagonists) based on LVEF. ✹✹ Implementation of the universal definition of HF requires the alignment between administrative tools, performance measures, administrative databases, registries, research initiatives, clinical practices, and the use of standardized terminologies. ✹✹ Clinicians and patients must be educated about new terminology and HF staging, particularly for the pre-HF stage, when screening and HF prevention strategies can be initiated.

References:1. Bozkurt B, Coats AJ, Tsutsui H, et al. Universal

definition and classification of heart failure: A report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure [published online ahead of print, 2021 Mar 1]. J Card Fail. 2021;S1071-9164(21)00050-6. doi:10.1016/j.cardfail.2021.01.022

2. Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur J Heart Fail. 2021;23(3):352-380. doi:10.1002/ejhf.2115


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2 Health Status Benefits of Mavacamten in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results from the EXPLORER-HCM Randomized Clinical Trial

John Spertus, MD, MPH, FAHA, FACC, Kansas City, MOConsultant Fees/Honoraria: Abbott Laboratories, CareDX Inc.,

Medtronic, NuPulse, Procyrion, Amgen Inc., AstraZeneca, Bayer, Copyright for SAQ, KCCQ and PAQ, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., MyoKardia, Novartis, United Healthcare; Office, Director, Trustee, or Other Fiduciary Role: Blue Cross Blue Shield of Kansas City; Other: Abbott Laboratories; Ownership Interest/Partnership/Principal: Health Outcomes Sciences; Research/Research Grants: American College of Cardiology Foundation

James C. Fang, MD, FACC, Park City, UTConsultant Fees/Honoraria: Abbott Laboratories, CareDX Inc.,

Medtronic, NuPulse, Procyrion, Boston Scientific; Data Safety Monitoring Board: Boehringer Ingelheim Pharmaceuticals, Inc., Capricor Therapeutics, Johnson & Johnson, National Institutes of Health; Other: ACI Clinical, American Heart Association, Amgen Inc., AstraZeneca, National Institutes of Health, Novartis, UpToDate; Research/Research Grants: National Institutes of Health

Correspondent: Sherry-Ann Brown, MD, PhD, FACC, FAHA, Milwaukee, WI

Take-home Messages:✹✹ Obstructive hypertrophic cardiomyopathy (HCM) is a genetic disease of sarcomeric gene mutations that leads to dynamic outflow obstruction and hypercontractility. ✹✹ Negative inotropic drugs (eg, verapamil, disopyramide) have been used to improve symptoms, function, and quality of life, as well as to prevent sudden cardiac death in patients with HCM. Surgical options (eg, myectomy) or alcohol septal ablation are considered when pharmacologic treatments have failed. ✹✹ The EXPLORER-HCM trial was a large, randomized clinical trial that tested the efficacy of mavacamten (a novel direct myosin inhibitor) versus placebo in patients with obstructive HCM. Investigators aimed to define patient-level benefits in symptoms, function, and quality of life through the Kansas City Cardiomyopathy Questionnaire (KCCQ) among patients with symptomatic and severely obstructive HCM treated with mavacamten. ✹✹ The KCCQ is a clinical outcome assessment tool used to measure symptoms, physical and social function, and quality of life in patients. It has been validated in patients with heart failure with reduced or preserved ejection fraction and valvular heart disease, but does not explicitly measure some of the other common symptoms of obstructive HCM, such as chest pain, palpitations, and lightheadedness. Nevertheless, the KCCQ was deemed relevant in psychometric validity to patients with obstructive HCM. ✹✹ The EXPLORER-HCM investigators also used the HCM Symptom Questionnaire, a disease-specific assessment tool created by the developers of mavacamten. This

instrument is still undergoing psychometric validation and analysis. Cost effectiveness was analyzed using EQ-5D utilities.✹✹ The KCCQ was administered at baseline, and at 6, 12, 18, and 30 weeks. Treatment was stopped at 30 weeks, and the KCCQ was repeated at 38 weeks. ✹✹ Although approximately 250 patients were enrolled in the trial, administrative and data collection errors resulted in completion of the KCCQ at baseline and at 30 weeks by slightly fewer than 100 patients (≈70% completion rate) in the mavacamten group. Extensive analyses were performed to ensure no bias was introduced.✹✹ Investigators found that at baseline, KCCQ scores were identical between those who received mavacamten and those who received placebo. At 6 weeks, the scores began to separate, and continued to separate until 30 weeks, with a mean difference in the overall summary score ≈9 points greater with mavacamten than with placebo — a highly statistically significant benefit. The proportion of patients with a change of >20 points on the KCCQ was 36% in the mavacamten group versus 15% in the placebo group (an estimated absolute difference of 21%, or a number needed to treat of 5).✹✹ At 38 weeks, there was no difference in KCCQ scores between the mavacamten and placebo groups. Once mavacamten was stopped, KCCQ scores returned to baseline.✹✹ It remains unclear which physiologic parameters and patient characteristics are most associated or predictive of benefits in health status with the use of mavacamten. The EXPLORER-HCM trial is being extended for an additional 5 years of follow-up.

Reference:1. Spertus JA, Fine JT, Elliott P, et al. Mavacamten

for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;397(10293):2467-2475. doi:10.1016/S0140-6736(21)00763-7

3 How Do I Interpret the Echo Results in HFpEF?

Jae K. Oh, MD, Rochester, MNConsultant Fees/Honoraria: Medtronic; Other: MedtronicJohn Gorcsan III, MD, FACC, Hershey, PAResearch/Research Grants: Biotronik, EBR Systems, GE Life Sciences,

Hitachi Aloka, Medtronic, Toshiba, V-WaveCorrespondent: Estefania Oliveros, MD, MSc, Philadelphia, PATake-home Messages:

✹✹ The diagnosis of heart failure with preserved ejection fraction (HFpEF) depends on the detection of increased filling pressure on echocardiography, primarily using the ratio of mitral inflow velocity to mitral annular early diastolic velocity (E/e’) and tricuspid regurgitation (TR) velocity.


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✹✹ Left atrial (LA) volume index is a helpful parameter, but hemodynamic data are more important to evaluate since LA volume index is often discordant with the final grading of diastolic function. 10% to 20% of normal individuals have an increased LA volume index, and some individuals with increased filling pressure may not have an elevated LA volume index. ✹✹ TR velocity assumes that pulmonary hypertension is secondary to elevated filling pressures. But some patients with pulmonary vascular disease have normal filling pressure. ✹✹ Pre- and postcapillary pulmonary hypertension is relatively rare (seen in ≈10% of patients in clinical practice). ✹✹ Left ventricular (LV) filling pressure in patients with significant pulmonary hypertension is usually low (ie, grade 1 diastolic dysfunction). ✹✹ Mitral annular early diastolic velocity can be elevated in patients with, eg, mitral annulus calcification, left bundle-branch block, conduction delay, hypertrophic cardiomyopathy, atrial fibrillation. Other parameters should be evaluated in order to assess filling pressure in these patients.✹✹ Most patients with HFpEF have reduced global longitudinal strain. LA strain imaging is useful for estimating LV filling pressure. Global LA reservoir strain values ≥40% during systole indicate normal function, while values ≤ 25% suggest elevated LV filling pressures. ✹✹ 40% to 50% of patients with HFpEF are found to have normal filling pressure at rest. Most of these patients develop symptoms with exertion, and can be evaluated with exercise echocardiography. ✹✹ Patients with dyspnea (with exercise or at rest) and a cardiac condition usually have elevated LV filling pressure, which can be reliably estimated on the basis of, eg, tissue Doppler findings, mitral inflow velocity, TR velocity. Patients with high filling pressure have worse prognosis than patients with ischemia with regional wall motion changes.✹✹ Echocardiography is useful for distinguishing HFpEF from HFpEF mimickers, such as cardiac amyloidosis, constrictive pericarditis, hypertrophic cardiomyopathy, valvular heart disease, and high-output heart failure.

References:1. Nagueh SF, Smiseth OA, Appleton CP, et al.

Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277-314. doi:10.1016/j.echo.2016.01.011

2. Shah AM, Cikes M, Prasad N, et al. Echocardiographic features of patients with heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol. 2019;74(23):2858-2873. doi:10.1016/j.jacc.2019.09.063

4 Conversations in Cardiology: Exercise Right Heart Catheterization

Paul Forfia, MD, Philadelphia, PAConsultant Fees/Honoraria: Actelion, Bayer, Gilead Sciences, United

TherapeuticsDonna Mancini, MD, New York, NYThis author has nothing to disclose.Sean P. Pinney, MD, FACC, New York, NYConsultant Fees/Honoraria: Abbott Laboratories, CareDX Inc.,

Medtronic, NuPulse, ProcyrionCorrespondent: Estefania Oliveros, MD, MSc, Philadelphia, PATake-home Messages:

✹✹ Right-sided heart catheterization is most commonly performed to evaluate and monitor patients for heart transplantation. It also useful for the assessment of patients hospitalized with acute decompensated heart failure who have hypertension and/or unclear volume status, or outpatients with symptoms that are out of proportion to physical examination findings. ✹✹ For most patients who present to the clinic, standard cardiopulmonary exercise testing performed before right heart catheterization provides sufficient information about the patient’s exercise limitations. However, some patients’ exercise capacity may not be as limited as expected in respect to their complaints and their right heart catheterization findings — those patients should undergo level 3 exercise stress testing for exercise-induced pulmonary hypertension and diastolic dysfunction. ✹✹ The use of exercise right heart catheterization to evaluate functional capacity and hemodynamics must be individualized and aimed at uncovering or clarifying a suspected diagnosis. It is not appropriate for patients with, eg, overt decompensated heart failure that is clearly caused by very severe pulmonary hypertension and right-sided heart failure. Exercise right heart catheterization may illuminate the predominant cause of functional limitation in patients with, eg, less severe pulmonary hypertension with other comorbidities, or mild phenotype of heart failure with preserved ejection fraction (HFpEF) and more severe symptoms. ✹✹ Exercise studies should be performed to look for exercise-induced pulmonary hypertension, elevated pulmonary vascular resistance in the setting of normal pulmonary artery wedge pressure, evidence of diastolic dysfunction (eg, increased pulmonary artery and pulmonary artery wedge pressures), and signs of worsening of mitral regurgitation (eg, increased Doppler signaling, increased V wave, increased pulmonary pressures).✹✹ With respect to the use of intravenous fluid challenges, Dr. Forfia feels that there are far better and more physiologic ways to interrogate the diastolic filling reserve and left-sided filling pressure reserve.


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✹✹ When using a supine bicycle ergometer on patients with HFpEF, placement of the feet in the pedals (ie, a leg-up position) often increases left atrial pressure. The finding can be noted, but is not regarded as a “stage of the assessment.” Clinicians should more carefully evaluate left- and right-sided filling pressures, pulmonary artery pressure, delta cardiac output, stroke volume, and delta pulmonary vascular resistance.✹✹ Most of the exercise studies performed in the catheterization laboratory are done while the patient is supine. Studies performed in the exercise laboratory allow for the patient to be upright. There are no significant differences in the directional changes and ultimate diagnoses between testing that uses supine exercise and testing that uses upright exercise. ✹✹ Level 3 stress testing can be used to assess pulmonary pressures during exercise in patients with a ventricular assist device. ✹✹ Implantable pressure sensors used for remote monitoring detect changes in pressure but do not provide a complete hemodynamic profile of the patient. Physicians must have a strong understanding of exercise physiology and exercise hemodynamics in order to appropriately apply information from implantable pressure and/or hemodynamic sensors to diagnostic and management decisions. ✹✹ In summary, standard diagnostic testing, a thorough patient history and physical examination, and standard cardiopulmonary exercise testing are sufficient for determining the causes of functional impairment in most patients. Exercise catheterization is appropriate for patients with an unclear diagnosis or competing diagnoses where further physiologic insight is needed. Sufficient training and knowledge are required to perform the test and to integrate the results in the overall management of the patient.

References:1. Reddy YNV, Olson TP, Obokata M, Melenovsky V,

Borlaug BA. Hemodynamic correlates and diagnostic role of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. JACC Heart Fail. 2018;6(8):665-675. doi:10.1016/j.jchf.2018.03.003

2. Rieth A, Richter MJ, Gall H, et al. Hemodynamic phenotyping based on exercise catheterization predicts outcome in patients with heart failure and reduced ejection fraction. J Heart Lung Transplant. 2017;36(8):880-889. doi:10.1016/j.healun.2017.02.022

DISC 2

1 A “Dispensary of Hope”: Transitional Care in Heart Failure

Connie White-Williams, PhD, RN, NE-BC, FAAN, Birmingham, AL

This author has nothing to disclose.Dipti Itchhaporia, MD, FACC, Newport Beach, CAResearch/Research Grants: Amgen Inc.Correspondent: Arjun Majithia, MD, Burlington, MATake-home Messages:

✹✹ Dr. White-Williams describes the clinic in Birmingham, AL, at which she helps provide transitional care services to underserved patients with heart failure. The nurse-led clinic is an interprofessional, collaborative practice involving members from nursing, social work, medicine, pharmacy, other health professions, and public health service teams who work together to devise a care plan for heart failure patients.✹✹ The Dispensary of Hope is a charitable medication distributor that provides reliable access to free or affordable medications through pharmacies and safety-net clinics. The medications are usually donated by pharmaceutical manufacturers. To qualify, patients cannot have any form of prescription coverage, and must be at or below 200% of the federal poverty line. ✹✹ Health system pharmacies involved in the Dispensary of Hope program “create a separate space” specifically for medications to be provided to underserved populations. ✹✹ Every patient who is discharged from the University of Alabama at Birmingham Hospital is given the opportunity to be referred to the clinic. Patients who are underserved (ie, patients without insurance coverage, patients who are underinsured, and patients who do not have a medical home to manage their heart failure) are managed and followed by the health care team at the clinic.✹✹ Since many of the patients at the clinic are faced with challenges when paying for medications, food, and bills, a program was developed to help them access their medications. The nurse-led team initiates a medication reconciliation process to ensure that patients are prescribed medications at discharge and that maintenance medications are appropriately titrated. ✹✹ Patients are extensively educated about their medication action plans so that they know how and when to take their medications. The use of pill boxes is a helpful strategy to keep track of doses.✹✹ Transportation is a social determinant of health and can be a barrier to accessing medications. Patients are provided bus passes to the clinic or pharmacy, and parking at the clinic is free.✹✹ Other patient assistance strategies include the use of low-cost pharmacies, coupons, and participation in pharmaceutical assistance programs.


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✹✹ Social workers and nurse practitioners work together to identify low-cost medications and all available resources for patients who do not fully qualify for pharmaceutical assistance programs, but are unable to afford their medications.✹✹ Measuring social determinants of health and implementing interventions can be challenging. Multiple instruments are available to help measure social determinants of health, and some are embedded into electronic medical records. Screening tools, such as the PRAPARE tool, can be used to assess, eg, food insecurity, medications, transportation, socioeconomic status.

References:1. Arnold ER, White-Williams C, Miltner RS, Hites

L, Su W, Shirey MR. Transitional care home visits among underserved patients with heart failure. Nurs Adm Q. 2020;44(3):268-279. doi:10.1097/NAQ.0000000000000426

2. White-Williams C, Clarkson EB, Shirey M, Bittner V. Caring for underserved patients with heart failure during the COVID-19 pandemic. J Health Care Poor Underserved. 2020;31(3):1061-1066. doi:10.1353/hpu.2020.0081

2 Supporting the Failing RV from Group I to Group II PH with Drugs: The Do’s and the Don’t’s

Robert P. Frantz, MD, FACC, Rochester, MNConsultant Fees/Honoraria: Actelion, Altavant, Gossamer Bio,

Liquidia, Shouti, UpToDate; Research/Research Grants: Acceleron Pharma, Bayer, Medtronic, United Therapeutics

Christopher B. Granger, MD, FACC, Durham, NCConsultant Fees/Honoraria: AbbVie, Inc., AstraZeneca, Bayer,

Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, Bristol Myers Squibb, Celecor, Espero, Janssen Pharmaceuticals, Inc., Medscape, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer, Phillips, Rhoshan, Roche; Research/Research Grants: Akros, Apple, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol Myers Squibb, Daiichi Sankyo, FDA, GlaxoSmithKline, Janssen Pharmaceuticals, Inc., Medtronic, National Institutes of Health, Novartis, Pfizer

Correspondent: Michelle D. Kelsey, MD, Durham, NCTake-home Messages:

✹✹ Pulmonary hypertension (PH) patients with right ventricular (RV) failure should undergo evaluation for hypoxemia with overnight oximetry and exercise testing. This is true whether the patient has group 1 PH (pulmonary arterial hypertension [PAH] without left-sided heart disease), or group 2 PH with left-sided involvement and elevated left-sided filling pressures that contribute to elevated pulmonary arterial (PA) pressures. ✹✹ In order to distinguish group 1 PH from group 2 PH, clinicians should evaluate the patient’s history and echocardiographic findings. An E/e’ ratio above 9 denotes possible diastolic dysfunction. Evaluating left

atrial size and the morphology of the heart can also help identify contributors of left heart disease. ✹✹ The H2FPEF score is a useful tool for assessing risk factors for heart failure with preserved ejection fraction (HFpEF), such as diabetes, older age, hypertension requiring at least 2 drugs, atrial fibrillation, and evidence of PH on echocardiography. ✹✹ In patients with heart failure with reduced ejection fraction (HFrEF), PH tends to respond well to afterload reduction on the left heart with, eg, nitroprusside, which may suggest that basic therapies (eg, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) can be used more aggressively. ✹✹ Prevention of RV failure is incredibly valuable in the management of patients with PAH and normal left ventricular function. Patients with PAH are often undertreated with guideline-directed medical therapy (GDMT). Combination or triple PAH therapy (including parenteral prostanoid therapy) can reduce pulmonary vascular resistance and allow for RV recovery. ✹✹ Diuretics should be used appropriately in patients with biventricular heart failure and isolated right-sided heart failure. The bioavailability of furosemide may be low in patients with right-sided congestion whose intestinal mucosa becomes engorged with fluid. Switching from furosemide to torsemide or bumetanide in combination with an aldosterone antagonist (eg, spironolactone) either in precapillary or mixed pre- and postcapillary PH with biventricular failure can be helpful. ✹✹ Patients with advanced heart failure, excessively elevated pulmonary vascular resistance, and PH with LV dysfunction may not be good candidates for heart transplantation because of increased risk for donor RV failure. In those cases, perform hemodynamic studies in the catheterization laboratory and a nitroprusside trial to determine whether PA pressures can be reduced. Patients with severely elevated PA pressure and pulmonary vascular resistance >4 Wood units should be evaluated in the intensive care unit and given intravenous (IV) diuretics. ✹✹ Milrinone plus IV diuretics can be used in patients with biventricular failure to reduce left heart filling pressure and increase pulmonary vasodilation. Pulmonary vasoconstriction is often reversible with proper management of wedge pressure and pulmonary vasodilation. ✹✹ Performing a ventilation/perfusion lung scan is helpful for detecting pulmonary emboli in, eg, older patients with HFpEF risk factors and worsening signs and symptoms (eg, shortness of breath). ✹✹ Since the management of group 1 PAH differs from that of group 2 PH, it is important to understand the physiology of PH in the patient and treat appropriately. Always evaluate PH patients for hypoxemia, use GDMT in order to optimize management and prevent complications, and recognize the adverse nature of RV failure in all forms of PH.


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References:1. Maron BA, Abman SH, Elliott CG, et al. Pulmonary

arterial hypertension: diagnosis, treatment, and novel advances. Am J Respir Crit Care Med. 2021;203(12):1472-1487. doi:10.1164/rccm.202012-4317SO

2. Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation. 2018;138(9):861-870. doi:10.1161/CIRCULATIONAHA.118.034646

3 Translating the Fourth Universal Definition of Myocardial Infarction into Clinical Documentation for Front-Line Clinicians and Health Systems

Abhinav Goyal, MD, MHS, FACC, Atlanta, GAThis author has nothing to disclose.Richard A. Chazal, MD, MACC, Fort Myers, FLThis author has nothing to disclose.Correspondent: Henry D. Huang, MD, FACC, Chicago, ILTake-home Messages:

✹✹ The Fourth Universal Definition of Myocardial Infarction Expert Consensus Document was published in 2018 as an effort to redefine myocardial infarction (MI) in alignment with biochemical and clinical findings. ✹✹ Correctly defining MI is important to improving patient care and to the avoidance of certain therapies, such as heparin, antiplatelet agents, and early catheterization in patients with type 2 MI or nonischemic myocardial injuries. ✹✹ Type 1 MI includes non–ST-segment elevation myocardial infarction (NSTEMI) with plaque rupture or plaque erosion. Type 2 MI is based on supply and demand mismatch. Nonischemic myocardial injuries include troponin elevations from myocardial injury not due to an ischemic mechanism. ✹✹ To meet the criteria for an MI, cardiac troponin levels must follow a rise and/or fall pattern. Though the consensus document does not specifically describe what constitutes a rise or fall, a 20% variation among measured values generally constitutes a significant change.✹✹ After determining the presence or likely presence of rising and/or falling cardiac enzymes, the clinician should assess for overt or objective evidence of myocardial ischemia, such as chest pain or shortness of breath not readily explained by other causes, acute ischemic changes on electrocardiography, and critical findings on nuclear imaging studies or coronary angiography.✹✹ Clinical context and critical illness often underlie type 1 and type 2 MI. For example, a patient with spontaneous chest pain without any potential provoking factors may have type 1 MI precipitated by plaque rupture. Provoking

factors to consider include gastrointestinal (GI) bleeding, anemia, and hypoxic respiratory failure.✹✹ Type 1 MI or NSTEMI is a principal diagnosis and usually the primary reason the patient presents to the hospital, whereas the diagnosis of type 2 MI is usually secondary to some other underlying process (eg, GI bleeding). ✹✹ Later this year, the National Center for Health Statistics in conjunction with the Centers for Disease Control and Prevention will be introducing new coding for nonischemic myocardial injury. ✹✹ In summary, “don’t jump the gun” with a diagnosis of NSTEMI when patients present to the hospital. Evaluate and document troponin levels (it may take ≈2 days to fully understand the clinical picture and reach a final diagnosis of type 1 or type 2 MI). Documentation of “suspected NSTEMI” implies type 1 MI, and should not be used to document suspected type 2 MI. Consistent documentation among hospital medicine physicians, cardiologists, and catheterization laboratory technicians is important.

Reference:1. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth

universal definition of myocardial infarction (2018) [published correction appears in Circulation. 2018 Nov 13;138(20):e652]. Circulation. 2018;138(20):e618-e651. doi:10.1161/CIR.0000000000000617

4 Taking Breast Cancer to Heart: Cardiovascular Prevention Strategies

Jo E. Rodgers, PharmD, BCPS, BCCP, FCCP, FHFSA, FAHA, Chapel Hill, NC

Research/Research Grants: Novartis Cindy L. Grines, MD, FACC, MSCAI, Johns Creek, GAConsultant Fees/Honoraria: Abiomed, Philips Volcano; Research/

Research Grants: Boston ScientificCorrespondent: Sherry-Ann Brown, MD, PhD, FACC, FAHA, Milwaukee, WI

Take-home Messages:✹✹ Chemotherapeutic anthracyclines (eg, doxorubicin, daunorubicin) and targeted biologic agents (eg, trastuzumab, pertuzumab) used to treat breast cancer are associated with increased risk for cardiomyopathy. ✹✹ Small, randomized controlled trials have looked at the potential cardioprotective effects of standard heart failure therapies, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers, as well as other interventions (eg, aldosterone receptor antagonists, statin therapy, exercise) among women undergoing breast cancer treatment. ✹✹ A recent study looked at ≈500 women with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer undergoing treatment with trastuzumab. Investigators aimed to determine whether an ACE


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inhibitor (lisinopril) or β-blocker (carvedilol 10 mg/day) could reduce the rate of trastuzumab-associated cardiotoxicity, compared with placebo. Patients were stratified by anthracycline use before randomization. The study found that cardiotoxicity and trastuzumab treatment interruptions were reduced in patients who received ACE inhibitor or β-blocker therapy. ✹✹ Meta-analyses reviewing randomized controlled trials using ACE inhibitors and β-blockers suggest that overall cardiac events and changes in left ventricular ejection fraction (LVEF) can be negated with ACE inhibitors and β-blockers. ✹✹ Most trials have looked at the end point of left ventricular ejection fraction as measured by echocardiography. There is a need for data about the effects of heart failure drugs on all-cause mortality and global longitudinal strain. ✹✹ There may be a potential role for statin therapy in the management of breast cancer. A large meta-analysis looking at 14 preclinical studies (nearly 80,000 breast cancer patients) found that HMG-CoA reductase inhibitors had a beneficial role in recurrence-free survival, overall survival, and cancer-specific survival. ✹✹ A major limitation of these meta-analyses is the degree of heterogeneity among the studies that were reviewed. The studies varied quite a bit in design, comorbidities of the participants, prevalence of cardiovascular risk factors, and duration of the trials (ranging from a few months to a year).✹✹ Guideline recommendations about the use of cardiac therapies in breast cancer patients vary among organizations. The National Cancer Comprehensive Network and the American Society of Clinical Oncology have not embraced the literature (primarily because of trial design), while some European organizations have. ✹✹ There is general agreement among guidelines that surveillance with echocardiography should be performed in patients receiving anthracycline therapy in conjunction with targeted HER2 therapies. Some guidelines also recommended monitoring biomarker levels. ✹✹ Evidence supports the role of guideline-directed medical therapy in the management of heart failure, but now there is mounting evidence that the benefit of these therapies can outweigh the risks, particularly among younger women undergoing aggressive, potentially cardiotoxic breast cancer therapies. ✹✹ The use of ACE inhibitors, ARBs, and β-blockers is reasonable in patients undergoing treatment of breast cancer who have substantial reductions in LVEF, cardiomyopathy, or risk factors for clinical or subclinical cardiomyopathy. ✹✹ Risk factors for cardiomyopathy, ischemia, or other forms of cardiotoxicity are: age >60 years, female sex, known cardiovascular disease or a high burden of cardiovascular risk factors or comorbidities, prior or current breast cancer treatment particularly with anthracyclines and radiation therapy.

References:1. Brown SA, Okwuosa TM, Barac A, Volgman AS.

The role of angiotensin-converting enzyme inhibitors and β-blockers in primary prevention of cardiac dysfunction in breast cancer patients. J Am Heart Assoc. 2020;9(2):e015327. doi:10.1161/JAHA.119.015327

2. Guglin M, Krischer J, Tamura R, et al. Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J Am Coll Cardiol. 2019;73(22):2859-2868. doi:10.1016/j.jacc.2019.03.495

3. Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. Int J Cancer. 2016;139(6):1281-1288. doi:10.1002/ijc.30185

5 JACC State-of-the-Art Review: Impact of Percutaneous Coronary Intervention on Outcomes in Patients with Heart Failure

Puja Parikh, MD, MPH, FACC, Stony Brook, NYConsultant Fees/Honoraria: Medtronic Roxana Mehran, MD, FACC, New York, NYConsultant Fees/Honoraria: Boston Scientific, Cine-Med Research

Institute, Janssen Pharmaceuticals, Inc.; Other: Elixir Medical, WebMD; Ownership Interest/Partnership/Principal: Applied Therapeutics, ControlRad, STEL; Research/Research Grants: Abbott Laboratories, Abiomed, AstraZeneca, Bayer, Beth Israel Deaconess Medical Center, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis, OrbusNeich

Correspondent: Maya Ignaszewski, MD, Chicago, ILTake-home Messages:

✹✹ Coronary artery disease (CAD) remains the most common cause of heart failure in the United States, accounting for nearly two-thirds of cases. Coronary artery bypass grafting (CABG) has long been the mainstay of treatment for patients with multivessel CAD and reduced ejection fraction (EF). But in this contemporary era of percutaneous coronary intervention (PCI), newer PCI optimization strategies are available — newer-generation drug-eluting stents, antiplatelet therapy, percutaneous mechanical circulatory support devices, and the use of intravascular imaging studies.✹✹ The underutilization of coronary angiography in patients hospitalized with acute heart failure correlates with low rates of revascularization with PCI in these patients. Coronary angiography is performed in only 10% to 15% of patients during the index hospitalization, and <20% of patients undergo coronary angiography within 90 days of their hospitalization. Rates of revascularization with PCI are even lower (<5% within the index hospitalization). ✹✹ Patients hospitalized with acute heart failure should undergo coronary angiography after diuresis. In patients with evidence of triple-vessel disease, the optimal management strategy (eg, performing viability studies or fractional flow reserve assessments to determine the need


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for revascularization or medical therapy alone) is unclear as more randomized trial data are needed.✹✹ Observational studies have demonstrated that PCI is certainly feasible in patients with moderately to severely reduced EF. ✹✹ Randomized controlled trials (eg, BARI 2D, FREEDOM) that compared PCI with CABG or with medical therapy in patients with stable CAD typically have excluded patients with severely reduced EF (or included only small number of heart failure patients). ✹✹ Observational studies and propensity score analyses that compare PCI with CABG in patients with heart failure with reduced ejection fraction (HFrEF) yield conflicting results, with a majority of studies suggesting greater long-term benefit with CABG than with PCI. ✹✹ There is also a lack of randomized data comparing PCI with medical therapy in patients with HFrEF. Observational studies have demonstrated that >50% patients with severely reduced EF experience varying degrees of improvement in EF after PCI, with greater improvements being correlated with treatment of a greater number of vessels. ✹✹ The REVIVED-BCIS2 trial, which aims to provide randomized data about the efficacy and safety of PCI in HFrEF patients, is currently underway. Investigators will compare a PCI strategy with optimal medical therapy vs medical therapy alone in ≈700 patients with EF ≤35%. ✹✹ Studies looking at the use of mechanical support devices in PCI patients with shock found no mortality benefit (mainly because of the heterogeneity in, eg, the definition of shock, systems of care for shock, and the timing of mechanical support implementation). Outside the setting of shock, mechanical support devices were found to have no effect on infarct size or mortality in patients with acute coronary syndrome undergoing PCI. ✹✹ Upcoming randomized controlled trials (eg, STEMI-DTU) will compare outcomes (eg, infarct size, mortality) in patients with ST-segment-elevation myocardial infarction undergoing PCI with Impella mechanical support.

Reference:1. Parikh PB, Bhatt DL, Bhasin V, et al. Impact of

percutaneous coronary intervention on outcomes in patients with heart failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021;77(19):2432-2447. doi:10.1016/j.jacc.2021.03.310

DISC 3

1 Telehealth and Patient Education: CardioSmart Is Here for You

Martha Gulati, MD, MS, FACC, FAHA, FASPC, FESC, Phoenix, AZ

This author has nothing to disclose.Matthew Martinez, MD, FACC, Morristown, NJConsultant Fees/Honoraria: Bristol Myers Squibb, Major League

SoccerCorrespondent: Payal Kohli, MD, FACC, Denver, COTake-home Messages:

✹✹ CardioSmart is a patient engagement program developed by the American College of Cardiology to support the patient-clinician relationship. CardioSmart enhances the health care experience in the clinic, but even more so during telehealth visits. ✹✹ CardioSmart provides tools for cardiologists to empower patients to become more informed and involved in their own care. Clinicians can direct patients to the CardioSmart website to learn more about their particular cardiac conditions and available treatments. ✹✹ CardioSmart provides effective tools for shared decision making for patients with, eg, atrial fibrillation, heart failure, or aortic stenosis. Tools such as infographics about medication use (eg, duration, efficacy, outcomes) or therapeutic devices are available. More tools and resources are being developed and added to the CardioSmart library so that health care teams can continue to build partnerships with their patients. ✹✹ Greater engagement through telehealth allows patients to play a larger role in their own health care. Providing patients with tools to learn more about their conditions before a health visit not only improves efficiency, but also improves the patient’s ability to engage in shared decision making. ✹✹ CardioSmart decision-making aids and visual aids are easy to understand, and may inform patients about, eg, reasons to change classes of medication, or how long a drug should be used before the patient can expect any benefit. ✹✹ Fact sheets, infographics, or action plans may be embedded in or attached to electronic health records or patient summaries.✹✹ Patients should have the opportunity to engage with other members of the health care team (eg, nurses, nurse practitioners) via telehealth.

References:1. Molinari G, Molinari M, Di Biase M, Brunetti

ND. Telecardiology and its settings of application: an update. J Telemed Telecare. 2018;24(5):373-381. doi:10.1177/1357633X16689432

2. Krauskopf PB. Relief central with coronavirus guidelines and CardioSmart Heart Explorer apps. J Nurse Pract. 2020;16(7):543-544. doi:10.1016/j.nurpra.2020.04.006


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2 Classification of Heart Failure According to Ejection Fraction

Carolyn Lam Su Ping, MBBS, PhD, FRCP, FAMS, FACC, FESC, Singapore

This author has nothing to disclose.Sidney C. Smith Jr., MD, MACC, Chapel Hill, NCThis author has nothing to disclose.Correspondent: Maya Ignaszewski, MD, Chicago, ILTake-home Messages:

✹✹ The recent publication of the Universal Definition of Heart Failure (a consensus opinion developed by multiple societies) proposed new classifications of heart failure (HF) according to ejection fraction (EF): HF with preserved EF (HFpEF) for patients with HF with left ventricular EF (LVEF) ≥50%, and HF with reduced EF (HFrEF) for patients with HF with LVEF ≤40%. The new classification also introduced new terminology — HF with mildly reduced EF — for patients with HF with LVEF 41% to 49%.✹✹ The recent Food and Drug Administration approval of sacubitril/valsartan included the expanded indication of HF with “less than normal” or “below normal” EF, with no reference to “preserved” or “reduced” EF on the labeling. ✹✹ This evolving HF terminology along with emerging evidence inspired Dr. Lam (and her colleague, Scott Solomon, MD) to propose revised nomenclature to define HF according to EF. ✹✹ Based on strong evidence, Dr. Lam agrees that the HFrEF class should remain for patients with HF with LVEF ≤40%. Based on accumulating evidence, neurohormonal blockers that benefit patients with HFrEF may also benefit patients with HF with mid-range EF; Dr. Lam agrees that the class HF with mildly reduced EF is appropriate for patients with HF with LVEF 41% to 49%.✹✹ HF with preserved EF was first coined in the CHARM-Preserved study to label patients with HF with LVEF ≥40%. Since contemporary nomenclature identifies patients with LVEF of 40% to 50% as HF with mildly reduced EF, Dr. Lam proposes classifying HF patients with truly normal EF as HF with normal EF. ✹✹ Sex-specific cut-offs should be used to classify normal EF. Since population-based studies and echocardiography guidelines demonstrate that normal EF is higher in women than in men at any given age, Dr. Lam proposes HF with normal EF for women with HF and LVEF ≥60%, or for men with HF with LVEF ≥55%. ✹✹ When systolic dysfunction is suspected (particularly in women), echocardiography findings should be evaluated to consider whether the patient may benefit from neurohormonal blockers. ✹✹ Patients with HF with normal EF should not be regarded as normal or healthy, and should undergo further work-up for, eg, high-output HF with anemia, presence of a shunt, amyloidosis, hypertrophic cardiomyopathy.

✹✹ The new definitions of HF are affecting enrollment in some clinical trials, and are likely to cause confusion before becoming incorporated into study designs and clinical practice. “But I do believe this is the correct direction, and we should embrace it,” says Dr. Lam.✹✹ Publication of new information, development of guidelines using new terminology (eg, “mildly reduced EF”), and education through HF congresses will promote agreement between various clinical groups and societies, and widen the use of these newer definitions.

References:1. Lam CSP, Solomon SD. Classification of heart failure

according to ejection fraction: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(25):3217-3225. doi:10.1016/j.jacc.2021.04.070

2. Bozkurt B, Coats AJ, Tsutsui H, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure [published online ahead of print, 2021 Mar 1]. J Card Fail. 2021;S1071-9164(21)00050-6. doi:10.1016/j.cardfail.2021.01.022

3 Moderate Aortic Stenosis in Patients with Heart Failure and Reduced Ejection Fraction

Marie-Annick Clavel, DVM, PhD, Quebec, CanadaThis author has nothing to disclose.Mirvat Alasnag, MB, BCH, FACC, Saudi Arabia, RiyadhThis author has nothing to disclose.Correspondent: Zaid I. Almarzooq, MBBCh, Boston, MATake-home Messages:

✹✹ Dr. Clavel and her group looked at patients from multicenter registries to determine the impact of moderate aortic stenosis on patients with heart failure with reduced ejection fraction (HFrEF). ✹✹ In the study, patients with moderate aortic stenosis had a moderate pressure gradient (<40 mm Hg) and an aortic valve area of 1.0 to 1.5 cm2 at rest or after dobutamine stress echocardiography. ✹✹ There were no significant differences in the medications and treatments between patients with moderate aortic stenosis and patients without moderate aortic stenosis. ✹✹ Although >70% of patients had coronary artery disease, aortic stenosis remains an independent predictor of outcomes in the study. Most of the patients had underwent revascularization before the study, and a small number of patients underwent revascularization during the study. ✹✹ Forty-four HFrEF patients with moderate aortic stenosis underwent transcatheter or surgical aortic valve replacement (AVR). The study concluded that AVR was associated with improved survival, mainly driven by transcatheter AVR.


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✹✹ Improvements in survival among patients who underwent transcatheter AVR, compared with surgical AVR can be explained by the less invasive nature of transcatheter procedures, and also by lower risk for prosthesis-patient mismatch after transcatheter AVR. ✹✹ The ongoing TAVR UNLOAD randomized controlled trial aims to compare outcomes of optimal heart failure management with those of transcatheter AVR among patients with HFrEF and moderate aortic stenosis.✹✹ Aortic valve calcification is a flow-independent marker of aortic stenosis severity, and is useful for identifying patients who may benefit from AVR. Patients with mild aortic stenosis are less likely to benefit from AVR than patients with moderate to severe aortic stenosis. ✹✹ Patients with HFrEF and moderate aortic stenosis (based on calcification scores) who remain symptomatic after treatment with optimal medical therapy should be referred for transcatheter AVR.

Reference:1. Jean G, Van Mieghem NM, Gegenava T, et al. Moderate

aortic stenosis in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021;77(22):2796-2803. doi:10.1016/j.jacc.2021.04.014

4 Myocardial Injury in COVID-19: What Echocardiography Has Revealed

Jonathan R. Lindner, MD, FACC, FASE, Portland, ORResearch/Research Grants: GE Life Sciences, Lantheus Medical

ImagingAnthony N. DeMaria, MD, MACC, San Diego, CAData Safety Monitoring Board: Celecor; Other: Hitachi, ResMed

Foundation; Research/Research Grants: Bracco, Trust; Speaker’s Bureau: Bracco, Zoll

Correspondent: Michael Mikolaj, MD, MPH, FACC, Chattanooga, TN

Take-home Messages:✹✹ Echocardiography is a useful modality for evaluating the heart in critically ill patients with COVID-19 infection, particularly those in the intensive care unit (ICU) with acute respiratory distress syndrome (ARDS) and diverse mechanisms of left and right ventricular function. ✹✹ During the early period of the COVID-19 pandemic, clinicians were performing echocardiography less often in order to limit patient exposure to possible infection, which gave rise to greater use of portable, handheld echocardiography devices on patients in isolation. The handheld systems do not have filters and are easier to clean. Some COVID-19 patients with complex mechanisms taking place in the heart required more advanced technologies. ✹✹ Many studies that looked at COVID-19 patients with right ventricular dysfunction and pulmonary hypertension on echocardiography suggest that prognosis varies

between patient populations (eg, hospitalized patients, patients with ARDS). ✹✹ The frequency of echocardiographic abnormalities and their prognostic implications vary between different COVID-19 patient population groups. For example, pulmonary hypertension tends to be a risk factor for advancing to the ICU and death, and right ventricular dysfunction and strain are very strong predictors of adverse outcomes for patients in the ICU.✹✹ Studies demonstrate that regional or global systolic dysfunction was extremely common in critically ill COVID-19 patients. One study reported left ventricular dysfunction in 40% to 50% of 305 ICU patients with ARDS. ✹✹ Several studies suggest that elevated troponin levels are more predictive of left ventricular dysfunction than is electrocardiography.✹✹ ARDS, parenchymal lung disease, and increased right ventricular afterload can cause right ventricular dysfunction in patients with COVID-19. ✹✹ There are 4 mechanisms that cause left ventricular dysfunction in patients with COVID-19. 1) Direct viral or inflammatory myocarditis due to an overexaggerated cytokine response. 2) Stress cardiomyopathy occurs in 3% to 5% of COVID-19 patients in the ICU. 3) Endothelialitis or vasculitis due to cytokine response or viral infection. 4) Thrombotic microangiopathy.✹✹ Dr. Lindner and his team is conducting an ongoing study using contrast ultrasonography with perfusion imaging performed at the bedside to help differentiate between the mechanisms of left ventricular dysfunction in COVID-19 patients. ✹✹ So far, the analysis has revealed that thrombi are not uncommon in patients with left ventricular dysfunction, as these patients are in a hypercoagulable state due to different mechanisms. And quite a few patients with unexplained perfusion abnormalities are believed to have a primary thrombotic angiopathy. ✹✹ One limitation is that there is a bidirectional relationship with COVID-19 in the heart. Since patients with preexisting cardiovascular disease are more likely to develop more severe manifestations, it is uncertain whether some of the findings (eg, wall motion abnormalities, perfusion defects) are new or old.✹✹ Abnormal global longitudinal strain (even with normal ejection fraction) is often predictive of an adverse course, especially when abnormalities are found on serial observations. Evaluation of strain can help differentiate pathophysiologic processes and uncover subtle cytokine-related cardiomyopathies and thrombotic microangiopathies.✹✹ Studies looking at the long-term prognostic implications of severe COVID-19 disease are underway. Several groups are looking at, eg, the resolution of pulmonary hypertension and left ventricular function in patients who survived COVID-19 disease. Other groups are using delayed enhanced magnetic resonance imaging to assess


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left ventricular dysfunction, while some are evaluating the responsiveness of cytokine-associated left ventricular dysfunction to traditional heart failure medications.

Reference:1. Giustino G, Croft LB, Stefanini GG, et al.

Characterization of myocardial injury in patients with COVID-19. J Am Coll Cardiol. 2020;76(18):2043-2055. doi:10.1016/j.jacc.2020.08.069

5 Clinical Utility and Age-Related Challenges of Cardiac Imaging in Older Patients

Jim Kirkpatrick, MD, FASE, FACC, Seattle, WAThis author has nothing to disclose.Jeroen J. Bax, PhD, MD, FACC, NetherlandsConsultant Fees/Honoraria: Abbott LaboratoriesCorrespondent: Akhil Narang, MD, FACC, Chicago, ILTake-home Messages:

✹✹ The elderly population is rapidly growing, and it is well known that older patients tend to have more cardiovascular disease — “the more we image, the more we’re going to find.” Before ordering imaging studies for older patients, clinicians must first consider how the results will affect management decisions and strategies. ✹✹ Prognostic imaging tests are often ordered for younger patients in order to determine the appropriateness to intervene with more invasive strategies. But in older patients, prognostic imaging studies often guide decisions that lead to less invasive strategies (eg, hospice or palliative care). ✹✹ Pharmacologic stress testing is an excellent option for older patients who are unable to undergo treadmill or bicycle stress testing.✹✹ When choosing an imaging modality for older patients, the clinician must consider frailty and the patient’s comorbidities. Patients who are frail, ie, lack physiologic reserve, tend to have comorbidities that put them at risk when they undergo imaging studies. Frail patients with renal dysfunction who undergo contrast imaging are at risk for nephropathy and other adverse effects. Frail patients with rheumatologic conditions may be unable to get up on the examination table. Wheelchair-bound patients can only be imaged by placing an echocardiography probe on their chest. For other patients, the amount of radiation exposure from the study must be considered. ✹✹ It remains unclear as to which imaging findings and test result values should be considered “normal” for older patients. More studies about the prognostic value of imaging tests and their clinical implications in older patients are needed. Emerging data is helping to define the range of normal values for healthy, older individuals. ✹✹ There are unique aspects of clinical care that must be considered when caring for older patients. Rather than focusing only on the patient’s cardiovascular

physiology and pathology, cardiologists must take on a broader perspective that considers the patient’s mobility, cognitive function, goals of care, values, and advanced directives.

References:1. Forman DE, de Lemos JA, Shaw LJ, et al.

Cardiovascular biomarkers and imaging in older adults: JACC Council perspectives. J Am Coll Cardiol. 2020;76(13):1577-1594. doi:10.1016/j.jacc.2020.07.055

2. Mehta N, Chokshi NP, Kirkpatrick JN. Cardiac imaging in the geriatric population: what do we think we know, and what do we need to learn?. Prog Cardiovasc Dis. 2014;57(2):204-214. doi:10.1016/j.pcad.2014.07.003

6 Pathophysiologic Relationships Between Arrhythmia and Cardiomyopathy: What Have We Learned So Far?

Brian Olshansky, MD, FACC, Iowa City, IAConsultant Fees/Honoraria: Lundbeck Inc., Respironics, Sanofi-

Aventis; Data Safety Monitoring Board: Amarin; Other: Boehringer Ingelheim Pharmaceuticals, Inc.

A. John Camm, MD, FACC, London, United KingdomConsultant Fees/Honoraria: Abbott Laboratories, Acesion, ARCA

biopharma, Inc., Astellas Pharma US, Bayer, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Incarda Therapeutics, Johnson & Johnson, Medtronic, Menarini, Milestone, OMEICOS, Pfizer, Portola, Radius, Richmond Pharmacology, Sanofi Aventis,Takeda; Data Safety Monitoring Board: Allergan, Inc., Anthos, Biotronik, GlaxoSmithKline

Correspondent: Anthony J. Mazzella, MD, Cary, NCTake-home Messages:

✹✹ There is a dynamic interplay between cardiomyopathy and arrhythmias. Cardiomyopathy can trigger a variety of arrhythmias, such as atrial fibrillation. But arrhythmias can worsen or create cardiomyopathies — arrhythmia-induced or modulated cardiomyopathy. Arrhythmia-induced cardiomyopathy can be reversed if the arrhythmia is treated early. ✹✹ Atrial fibrillation, atrial tachycardia, persistent supraventricular tachycardia (eg, permanent junctional reciprocating tachycardia), idiopathic ventricular tachycardia, and ventricular pacing can induce or modulate cardiomyopathy. But atrial fibrillation and premature ventricular contractions (PVCs) are most commonly associated with cardiomyopathy. ✹✹ The more innocuous arrhythmias tend to put the patient at greater risk because the patient does not recognize that the arrhythmias are ongoing. By the time the manifestations become problematic, the patient may have already developed congestive heart failure. ✹✹ In some cases, the arrhythmia occurs secondary to the cardiomyopathy. But in cases in which the arrhythmia is persistent at a fast rate (eg, persistent atrial fibrillation of >110 beats per minute at rest), or the density of the PVCs


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is high (eg, 15%-20% of total beats), then the arrhythmia should be addressed as an important cause of heart failure. ✹✹ Atrial fibrillation is an unlikely driver of heart failure in patients with controlled heart rates and normal sinus rhythm. ✹✹ Arrhythmia-induced cardiomyopathy can take a long time to develop. But heart failure can occur suddenly in patients in which the arrhythmia was corrected, but then recurs. An underlying remodeling process involving cytoskeletal and cellular changes takes place. The persistent remodeling can lead to ventricular hypertrophy after correction of the arrhythmia, as well as changes in other areas that are not easily measured by ejection fraction, such as the sarcoplasmic reticulum. Therefore, it is important to address arrhythmia-induced cardiomyopathy before structural remodeling takes place.✹✹ Management of a patient with PVCs and left ventricular impairment should begin with determining the presence of underlying structural disease and prevalence and frequency of the arrhythmia, while keeping in mind that there are multiple mechanisms of heart failure in patients with PVCs (eg, change in ventricular activation). In some cases, magnetic resonance imaging (MRI) to look for fibrosis or other underlying disease might be useful. A patient with some other cause of fibrosis or cardiomyopathy may become worse if they have PVCs. ✹✹ Not every patient with a high density of PVCs develops cardiomyopathy, but frequent PVCs are a red flag in patients with cardiomyopathy and congestive heart failure. ✹✹ Management of a patient with PVCs and class II heart failure includes MRI and cardiac catheterization, depending on the patient’s risk factors, age, and comorbid conditions. After looking for underlying disease, the PVCs should be treated with ablation or pharmacologic suppression therapy. The patient should then be reevaluated for heart failure and cardiomyopathy. Multicenter data show that most patients who present with PVC-induced cardiomyopathy improve after undergoing ablation therapy. ✹✹ Rate control therapy can be a very important strategy for patients with persistent atrial fibrillation. The use of atrioventricular junction ablation with pacemakers or implantable cardioverter defibrillators can improve outcomes. But it is important to have normal ventricular activation through the His-Purkinje system, and to have atrial contraction as well. It is best to also control rhythm. Dr. Olshansky feels that rhythm control is superior to rate control once patients have an arrhythmia-induced cardiomyopathy. ✹✹ In summary, heart failure and arrhythmias can coexist, and arrhythmias can cause heart failure. Persistent arrhythmia in a patient with heart failure is a red flag and must be treated. Treatment can reverse the cardiomyopathy. Patients should be managed early, before cardiomyopathy sets in and cardiac remodeling occurs.

Reference:1. Gopinathannair R, Dhawan R, Lakkireddy DR, et al.

Predictors of myocardial recovery in arrhythmia-induced cardiomyopathy: a multicenter study. J Cardiovasc Electrophysiol. 2021;32(4):1085-1092. doi:10.1111/jce.14963

7 Primary Prevention and Statins in Adults Over 75: Should You Stop Now?

Karen P. Alexander, MD, Durham, NCThis author has nothing to disclose.Annabelle S. Volgman, MD, FACC, Chicago, ILThis author has nothing to disclose.Correspondent: Taimur Safder, MD, MPH, Dallas, TXTake-home Messages:

✹✹ Since lipid levels typically do not change from year to year in adults over 75 who have no major health status changes, it is probably unnecessary to take annual lipid measurements. There are no United States Preventive Services Task Force or American College of Cardiology/American Heart Association recommendations to check lipid levels annually in adults over 75 years of age.✹✹ Most patients over 75 who are using statin therapy for primary prevention were started on statin therapy before they were 75. Very few (<2%) patients initiate statin therapy after age 75. It remains unclear whether statin therapy should be initiated or continued in patients over 75 (a large study is underway). ✹✹ Older adults who are living longer free of cardiovascular disease are at risk for cognitive impairment, dementia, and disability. More than 50% of individuals over 75 have cognitive impairment and/or frailty.✹✹ There appears to be a link between cognitive impairment and cardiovascular risk factors. In some regions of the United States, the geographic incidence of cognitive impairment and frailty largely matches the geographic incidence of obesity, diabetes, and hypertension. The rates of cognitive impairment and other cardiovascular risk factors are increased in the Stroke Belt, the Southern region of the United States where the risk for stroke is higher for the general population than it is in other areas of the country.✹✹ Subclinical cardiovascular disease, as evidenced by coronary artery calcium scores, predicts future development of cognitive impairment and dementia — likely mediated through vascular cognitive impairment. Statin therapy could potentially prevent ischemic stroke, another contributor to dementia over time. Effective vascular prevention may improve cognitive lifespan.✹✹ Does statin therapy cause memory loss? The PROSPER randomized trial found no adverse effects on cognitive function among patients on statin therapy in a trial setting. Small studies looking at patients with known dementia who were randomized to statin or placebo saw


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slower progression of cognitive decline in the patients who were randomized to statin therapy. Most of the concerns related to cognitive impairment with statin use are based on spontaneous reports of time-limited episodes of cognitive impairment. ✹✹ Statin therapy should be paused or stopped in patients who develop elevations in liver enzyme levels. Patients should undergo further evaluation. ✹✹ Recent trials (eg, SAMSON, StatinWISE) that looked at patients with muscle side effects (eg, muscle aches) who were randomized to statin therapy, placebo, or no pill, found that many of the adverse effects were related to the nocebo effect. “Even though about 10% of muscle side effects are definitely there, a vast majority are probably related to just the act of taking a pill and the expectation tied to that,” says Dr. Alexander. Patients should be educated about the side effects of statin therapy. ✹✹ The PREVENTABLE trial, a large, ongoing study aimed at determining cognitive and cardiovascular benefits of statin therapy in adults over 75 is underway. Investigators are currently recruiting older adults without dementia and no indications for statin therapy (eg, no history of stroke or myocardial infarction). Information is available at preventabletrial.org.

References:1. Rostamian S, de Haan S, van der Grond

J, et al. Cognitive function in dementia-free subjects and survival in old age: the PROSPER study. Am J Med. 2019;132(12):1466-1474.e4. doi:10.1016/j.amjmed.2019.06.001

2. Herrett E, Williamson E, Brack K, et al. The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs. Health Technol Assess. 2021;25(16):1-62. doi:10.3310/hta25160

3. Wood FA, Howard JP, Finegold JA, et al. N-of-1 trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med. 2020;383(22):2182-2184. doi:10.1056/NEJMc2031173

volume 53, issue 10 october 2021 - audio-digest.org

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