Publications by authors named "Michelle Kittleson"

170 Publications

Biology or Disparity? Untangling Racial Differences in Val122Ile Transthyretin Cardiac Amyloidosis.

J Card Fail 2022 Jan 15. Epub 2022 Jan 15.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.cardfail.2022.01.004DOI Listing
January 2022

Long-term outcomes after heart transplantation using ex vivo allograft perfusion in standard risk donors: A single-center experience.

Clin Transplant 2022 Jan 14:e14591. Epub 2022 Jan 14.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Introduction: The Organ Care System (OCS) is an ex vivo perfusion platform for donor heart preservation. Short/mid-term post-transplant outcomes after its use are comparable to standard cold storage (CS). We evaluated long-term outcomes following its use.

Methods: Between 2011 and 2013, 38 patients from a single center were randomized as a part of the PROCEED II trial to receive allografts preserved with CS (n = 19) or OCS (n = 19). Endpoints included 8-year survival, survival free from graft-related deaths, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejections.

Results: Eight-year survival was 57.9% in the OCS group and 73.7% in the CS group (p = .24). Freedom from CAV was 89.5% in the OCS group and 67.8% in the CS group (p = .13). Freedom from NF-MACE was 89.5% in the OCS group and 67.5% in the CS group (p = .14). Eight-year survival free from graft-related death was equivalent between the two groups (84.2% vs. 84.2%, p = .93). No differences in rejection episodes were observed (all p > .5).

Conclusions: In select patients receiving OCS preserved allografts, late post-transplant survival trended lower than those transplanted with an allograft preserved with CS. This is based on a small single-center series, and larger numbers are needed to confirm these findings.
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http://dx.doi.org/10.1111/ctr.14591DOI Listing
January 2022

The Role of Echocardiography in the Management of Heart Transplant Recipients.

Diagnostics (Basel) 2021 Dec 11;11(12). Epub 2021 Dec 11.

Heart Failure Unit, Department of Cardiology, AORN dei Colli-Monaldi Hospital, 80131 Naples, Italy.

Transthoracic echocardiography is the primary non-invasive modality for the investigation of heart transplant recipients. It is a versatile tool that provides comprehensive information on cardiac structure and function. Echocardiography is also helpful in diagnosing primary graft dysfunction and evaluating the effectiveness of therapeutic approaches for this condition. In acute rejection, echocardiography is useful with suspected cellular or antibody-mediated rejection, with findings confirmed and quantified by endomyocardial biopsy. For identifying chronic rejection, ultrasound has a more significant role and, in some specific patients (e.g., patients with renal failure), it may offer a role comparable to coronary angiography to identify cardiac allograft vasculopathy. This review highlights the usefulness of echocardiography in evaluating normal graft function and its role in the management of heart transplant recipients.
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http://dx.doi.org/10.3390/diagnostics11122338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699946PMC
December 2021

Post-transplantation outcomes of sensitized patients receiving durable mechanical circulatory support.

J Heart Lung Transplant 2021 Nov 18. Epub 2021 Nov 18.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Sensitization, defined as the presence of circulating antibodies, presents challenges, particularly in patients undergoing heart transplantation (HTx) bridged with durable mechanical circulatory support (MCS). We aimed to investigate the post-transplantation outcomes of sensitized MCS patients.

Methods: Among 889 consecutively enrolled heart transplant (HTx) recipients between 2010 and 2018, 86 (9.7%) sensitized MCS patients (Group A) were compared with sensitized non-MCS patients (Group B, n = 189), non-sensitized MCS patients (Group C, n = 162), and non-sensitized non-MCS patients (Group D, n = 452) regarding post-HTx outcomes, including the incidence of primary graft dysfunction (PGD), 1-year survival, and 1-year freedom from antibody-mediated rejection (AMR).

Results: Sensitized MCS patients (Group A) showed comparable rates of PGD, 1-year survival, and 1-year freedom from AMR with Groups C and D. However, Group A showed significantly higher rates of 1-year freedom from AMR (95.3% vs 85.7%, p = 0.02) and an earlier decline in panel-reactive antibody (PRA) levels (p < 0.01) than sensitized non-MCS patients (Group B). Desensitization therapy effectively reduced the levels of PRA in both Groups A and B. When Group A was further divided according to the presence of preformed donor-specific antibodies (DSA), patients with preformed DSA showed significantly lower rates of 1-year freedom from AMR than those without (84.2% vs 98.5%, p = 0.01).

Conclusions: Sensitized MCS patients showed significantly lower rates of AMR and an earlier decline in PRA levels following HTx than sensitized non-MCS patients. Removal of MCS at the time of transplantation might underlie these observations.
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http://dx.doi.org/10.1016/j.healun.2021.11.010DOI Listing
November 2021

Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors Among Medicare Beneficiaries Hospitalized for Heart Failure.

J Card Fail 2021 Nov 14. Epub 2021 Nov 14.

Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles, Los Angeles, California. Electronic address:

Background: The sodium-glucose cotransporter-2 (SGLT-2) inhibitors form the latest pillar in the management of heart failure with reduced ejection fraction (HFrEF) and appear to be effective across a range of patient profiles. There is increasing interest in initiating SGLT-2 inhibitors during hospitalization, yet little is known about the putative benefits of this implementation strategy.

Methods: We evaluated Medicare beneficiaries with HFrEF (≤ 40%) hospitalized at 228 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry in 2016 who had linked claims data for ≥ 1 year postdischarge. We identified those eligible for dapagliflozin under the latest U.S. Food and Drug Administration label (excluding estimated glomerular filtration rates < 25 mL/min per 1.73 m, dialysis and type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age ≥ 75 years, gender, race, hospital region, kidney function, diabetes status, triple therapy). We then projected the potential benefits of implementation of dapagliflozin based on the risk reductions observed in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial.

Results: Among 7523 patients hospitalized for HFrEF, 6576 (87%) would be candidates for dapagliflozin (mean age 79 ± 8 years, 39% women, 11% Black). Among eligible candidates, discharge use of β-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+β-blocker+MRA) was recorded in 88%, 64%, 29%, 3%, and 20%, respectively. Among treatment-eligible patients, the 1-year incidence (95% CI) of mortality was 37% (36-38%) and of HF readmission was 33% (32-34%), and each exceeded 25% across all key subgroups. Among 1333 beneficiaries eligible for dapagliflozin who were already on triple therapy, the 1-year incidence of mortality was 26% (24%-29%) and the 1-year readmission due to HF was 30% (27%-32%). Applying the relative risk reductions observed in DAPA-HF, absolute risk reductions with complete implementation of dapagliflozin among treatment-eligible Medicare beneficiaries are projected to be 5% (1%-9%) for mortality and 9% (5%-12%) for HF readmission by 1 year. The projected number of Medicare beneficiaries who would need to be treated for 1 year to prevent 1 death is 19 (11-114), and 12 (8-21) would need to be treated to prevent 1 readmission due to HF.

Conclusions: Medicare beneficiaries with HFrEF who are eligible for dapagliflozin after hospitalization due to HF, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. If the benefits of reductions in death and hospitalizations due to HF observed in clinical trials can be fully realized, the absolute benefits of implementation of SGLT-2 inhibitors among treatment-eligible candidates are anticipated to be substantial in this high-risk postdischarge setting.
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http://dx.doi.org/10.1016/j.cardfail.2021.11.010DOI Listing
November 2021

Innovations in Heart Transplantation: A Review.

J Card Fail 2021 Nov 6. Epub 2021 Nov 6.

Department of Medicine, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Advanced heart failure affects tens of thousands of people in the United States alone with high morbidity and mortality. Cardiac transplantation offers the best treatment strategy, but has been limited historically by donor availability. Recently, there have been significant advances in organ allocation, donor-recipient matching, organ preservation, and expansion of the donor pool. The current heart allocation system prioritizes the sickest patients to minimize waitlist mortality. Advances in donor organ selection, including predicted heart mass calculations and more sophisticated antibody detection methods for allosensitized patients, offer more effective matching of donors and recipients. Innovations in organ preservation such as with organ preservation systems have widened the donor pool geographically. The use of donors with hepatitis C is possible with the advent of effective direct-acting antiviral agents to cure donor-transmitted hepatitis C. Finally, further expansion of the donor pool is occurring with the use of higher risk donors with advanced age, medical comorbidities, and left ventricular dysfunction and advances in donation after circulatory death. This review provides an update on the new technologies and transplantation strategies that serve to widen the donor pool and more effectively match donors and recipients so that heart transplant candidates may derive the best outcomes from heart transplantation.
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http://dx.doi.org/10.1016/j.cardfail.2021.10.011DOI Listing
November 2021

Symptomology following mRNA vaccination against SARS-CoV-2.

Prev Med 2021 12 20;153:106860. Epub 2021 Oct 20.

Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.
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http://dx.doi.org/10.1016/j.ypmed.2021.106860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527734PMC
December 2021

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

J Heart Lung Transplant 2022 Jan 16;41(1):104-112. Epub 2021 Sep 16.

Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Introduction: Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory.

Methods: REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook.

Results: Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook.

Conclusions: Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.
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http://dx.doi.org/10.1016/j.healun.2021.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742755PMC
January 2022

Practice Patterns and Patient Outcomes After Widespread Adoption of Remote Heart Failure Care.

Circ Heart Fail 2021 10 30;14(10):e008573. Epub 2021 Sep 30.

Smidt Heart Institute (N.Y., P.G.B., Y.E., S.C., J.E.E., M.M.K.), Cedars-Sinai Medical Center, Los Angeles, CA.

Background: An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes.

Methods: We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes.

Results: Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18-0.22] video versus in-person, 0.18 [0.17-0.19] telephone versus in-person) or prescribe β-blockers (0.82 [0.68-0.99], 0.35 [0.26-0.47]), mineralocorticoid receptor antagonists (0.69 [0.50-0.96], 0.48 [0.35-0.66]), or loop diuretics (0.67 [0.53-0.85], 0.45 [0.37-0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40-0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14-2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97-1.86]) and hospitalizations (1.36 [0.98-1.89]).

Conclusions: Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530957PMC
October 2021

The effects of donor-specific antibody characteristics on cardiac allograft vasculopathy.

Clin Transplant 2021 Dec 28;35(12):e14483. Epub 2021 Oct 28.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Cardiac allograft vasculopathy (CAV) causes late graft dysfunction and post-transplant mortality. Currently, the effects of different donor-specific antibodies (DSA) on the severity of CAV remain unclear.

Method: We evaluated 526 adult heart transplant recipients at a single center between January 2010 and August 2015. Subjects were divided into those with DSA (n = 142) and those without DSA (n = 384, control). The DSA group was stratified into persistent DSA (n = 34), transient DSA (n = 105), 1:8 dilution DSA (n = 45), complement-binding (C1q) DSA (n = 36), Class I DSA (n = 37), and Class II DSA (n = 105). The primary outcome was the incidence of moderate-to-severe CAV (CAV 2/3) at 5-year follow-up.

Results: Subjects with persistent DSA, 1:8 dilution DSA, and C1q DSA had higher incidence of CAV 2/3 compared the control group (17.6%, 13.3%, and 16.7% vs. 3.1%, respectively; P≤ .001). The incidence of CAV 2/3 between subjects with transient DSA and the control group was similar (2.8% vs. 3.1%; P = .888). Subjects with Class II DSA also had higher incidence of CAV 2/3 (7.6% vs. 3.1%; P = .039).

Conclusion: DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. These DSA characteristics may prognosticate disease and warrant consideration for treatment.
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http://dx.doi.org/10.1111/ctr.14483DOI Listing
December 2021

Right Heart Catheterization in Patients with Advanced Heart Failure: When to Perform? How to Interpret?

Heart Fail Clin 2021 Oct 22;17(4):647-660. Epub 2021 Jul 22.

Heart Failure and Heart Transplant Program, IRCCS Policlinico di Sant'Orsola, Building 25 via Massarenti, 9, 40138 Bologna, Italy. Electronic address:

Right heart catheterization is an established cornerstone of advanced heart failure management, as a clear understanding of the patient's hemodynamic status offers insight into diagnosis, prognosis, and management. In this review, the authors will describe the role of right heart catheterization in the diagnosis and management of shock, in the context of left ventricular assist devices, in the assessment of heart transplant candidacy, and also explore future directions of implantable monitoring devices for pulmonary artery and left atrial pressure monitoring.
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http://dx.doi.org/10.1016/j.hfc.2021.05.009DOI Listing
October 2021

Donation after Circulatory Death: Extending the Boundaries of this New Frontier.

J Heart Lung Transplant 2021 11 10;40(11):1419-1421. Epub 2021 Aug 10.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

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http://dx.doi.org/10.1016/j.healun.2021.07.029DOI Listing
November 2021

Outcomes of cardiogenic shock with autoimmune rheumatological disorders.

Cardiovasc Revasc Med 2021 Aug 8. Epub 2021 Aug 8.

Division of Cardiology, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, United States of America.

Aims: Data on cardiogenic shock (CS) in autoimmune diseases (AID) is limited. Our study aims to evaluate in-hospital outcomes of CS in hospitalized patients with underlying AID compared with patients without AID.

Methods: The National Inpatient Sample (NIS) database years 2011-17 was used to identify hospitalizations for CS. We retrospectively compared in-hospital outcomes of CS in patients with underlying AID versus non-AID.

Results: Of 863,239 patients diagnosed with CS, 23,127 (2.7%) had underlying AID. The AID population was older with more women and African American patients (P < 0.001 for all). There was a significant increase in in-hospital mortality in patients with AID vs non-AID that persisted after adjustment for demographics, comorbidities, insurance, socioeconomic status and hospital characteristics (38.3% vs 36.3%, aOR 1.06; 95% CI: 1.02-1.09, P = 0.001). Patients with AID had a lower rate of respiratory complications (11.5% vs 13.1%), acute stroke (6.0% vs 6.8%), use of mechanical circulatory support (12.0% vs 14.5%) and discharge to an outside facility (29.1% vs 28.8%) (P ≤ 0.001 for all). Using multivariable logistic regression, we identified female gender, Native American ethnicity, heart failure, coagulopathy, pulmonary circulation disorders, metastatic cancer, and fluid and electrolytes disorders as independent predictors of mortality in patients with AID who were diagnosed with CS.

Conclusion: Patients with AID hospitalized with CS have increased mortality which may be related to their underlying disease process and lack of effective disease-directed therapy for CS related to AID.
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http://dx.doi.org/10.1016/j.carrev.2021.08.007DOI Listing
August 2021

Eculizumab for antibody-mediated rejection in heart transplantation: A case-control study.

Clin Transplant 2021 Dec 23;35(12):e14454. Epub 2021 Sep 23.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Complement inhibition offers a novel treatment approach for antibody-mediated rejection (AMR). We examined patients with hemodynamic compromise AMR 2010-2020, comparing eight patients supplemented with eculizumab to 10 patients without; administration was at the treating physician's discretion. There were no significant differences between groups though eculizumab patients had a non-significantly higher inotrope score (208.8 mcg/kg/min vs. 2.6 mcg/kg/min; P = .22), more extracorporeal membrane oxygenation (ECMO) (62.5% vs. 20%; P = .066), and worse 1-year survival (37.5% vs. 60%; P = .63). The role of eculizumab is uncertain in AMR; multicenter collaborative studies are essential to better define its role.
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http://dx.doi.org/10.1111/ctr.14454DOI Listing
December 2021

Heart Transplantation for Adriamycin Cardiomyopathy: The Plural of Anecdote and the Power of Registries.

JACC CardioOncol 2021 Jun 15;3(2):302-304. Epub 2021 Jun 15.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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http://dx.doi.org/10.1016/j.jaccao.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352018PMC
June 2021

Advanced heart failure and heart transplantation in adult congenital heart disease in the current era.

Clin Transplant 2021 Nov 12;35(11):e14451. Epub 2021 Sep 12.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center.

Methods: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery.

Results: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21).

Conclusion: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.
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http://dx.doi.org/10.1111/ctr.14451DOI Listing
November 2021

Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.

J Heart Lung Transplant 2021 09 10;40(9):970-980. Epub 2021 Jun 10.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). The International Society for Heart and Lung Transplantation (ISHLT) subdivides PGD into 3 grades of increasing severity. Most studies have assessed risk factors for PGD without distinguishing between PGD severity grade. We sought to identify recipient, donor and surgical risk factors specifically associated with mild/moderate or severe PGD.

Methods: We identified 734 heart transplant recipients at our institution transplanted between January 1, 2012 and December 31, 2018. PGD was defined according to modified ISHLT criteria. Recipient, donor and surgical variables were analyzed by multinomial logistic regression with mild/moderate or severe PGD as the response. Variables significant in single variable modeling were subject to multivariable analysis via penalized logistic regression.

Results: PGD occurred in 24% of the cohort (n = 178) of whom 6% (n = 44) had severe PGD. One-year survival was reduced in recipients with severe PGD but not in those with mild or moderate PGD. Multivariable analysis identified 3 recipient factors: prior cardiac surgery, recipient treatment with ACEI/ARB/ARNI plus MRA, recipient treatment with amiodarone plus beta-blocker, and 3 surgical factors: longer ischemic time, more red blood cell transfusions, and more platelet transfusions, that were associated with severe PGD. We developed a clinical risk score, ABCE, which provided acceptable discrimination and calibration for severe PGD.

Conclusions: Risk factors for mild/moderate PGD were largely distinct from those for severe PGD, suggesting a differing pathophysiology involving several biological pathways. Further research into mechanisms underlying the development of PGD is urgently needed.
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http://dx.doi.org/10.1016/j.healun.2021.06.002DOI Listing
September 2021

Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

J Am Heart Assoc 2021 07 10;10(14):e019901. Epub 2021 Jul 10.

Feinberg School of Medicine Northwestern University Chicago IL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (=0.007) and less burden by both time spent (<0.0001) and difficulty (=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (=0.034) and being a married caregiver (=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; =0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; =0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.
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http://dx.doi.org/10.1161/JAHA.120.019901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483456PMC
July 2021

Covid-19 in recipients of heart and lung transplantation: Learning from experience.

J Heart Lung Transplant 2021 09 9;40(9):948-950. Epub 2021 Jun 9.

Heart Failure and Transplant Program, IRCCS Policlinico di Sant'Orsola, Bologna, Italy.

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http://dx.doi.org/10.1016/j.healun.2021.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188768PMC
September 2021

Mechanical Circulatory Support as a Bridge-to-Transplant Candidacy: When Does It Work?

ASAIO J 2021 Jun 1. Epub 2021 Jun 1.

From the Departments of Cardiology and Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai, Los Angeles, California.

Durable mechanical circulatory support (dMCS) devices can be offered as a bridge-to-transplant (BTT) or as a bridge-to-candidacy (BTC) strategy for candidates with contraindications to transplant listing, including pulmonary hypertension (BTC-PH), morbid obesity (BTC-Obes), social issues (BTC-Soc), or chronic illness (BTC-Illness). An understanding of the trajectory of BTC patients could guide future triage of advanced heart failure patients who are not candidates for transplantation. We performed a retrospective review all patients who underwent dMCS implantation as either BTT (206 patients) or BTC (114 patients) at our center from January 1, 2010, to March 31, 2020. There was no significant difference in mortality between BTC patients and BTT patients. Compared with the BTT group, significantly more patients in the BTC-PH group were transplanted (81% vs. 63%; p < 0.05) and significantly fewer patients in the BTC-Obes group (44%; p < 0.05) and BTC-Soc group (39%; p < 0.05) were transplanted. Additionally, the readmission rate was higher for those in the BTC-Obes (6.2 vs. 2.1; p < 0.05) and BTC-Soc (3.9 vs. 2.1; p < 0.05) groups. Bridge-to-candidacy patients generally had poorer post-dMCS trajectories than BTT patients. Centers should not be dissuaded from pursuing a BTC strategy for qualified patients; however, careful consideration of potential adverse outcomes is necessary.
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http://dx.doi.org/10.1097/MAT.0000000000001500DOI Listing
June 2021

Kidney Function and Outcomes in Patients Hospitalized With Heart Failure.

J Am Coll Cardiol 2021 07 11;78(4):330-343. Epub 2021 May 11.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/mvaduganathan.

Background: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function.

Objectives: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction.

Methods: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality.

Results: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m (interquartile range: 34 to 72 ml/min/1.73 m), 234,332 (64%) had eGFR <60 ml/min/1.73 m, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m or dialysis (p < 0.001). "Triple therapy" with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (p = 0.045).

Conclusions: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.
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http://dx.doi.org/10.1016/j.jacc.2021.05.002DOI Listing
July 2021

Intersection of Heart Failure and Pregnancy: Beyond Peripartum Cardiomyopathy.

Circ Heart Fail 2021 05 13;14(5):e008223. Epub 2021 May 13.

Division of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (M.M.K.).

Heart failure (HF) is a leading cause of morbidity and mortality in pregnant women in the United States. Although peripartum cardiomyopathy is the most common diagnosis for pregnant women with HF, women with preexisting cardiomyopathies and systolic dysfunction are also at risk as the hemodynamic demands of pregnancy can lead to decompensation, arrhythmia, and rarely death. The differential diagnosis of HF in pregnancy is broad and includes Takotsubo or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, such as familial cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or left ventricular noncompaction. This review will explore the implications of pregnancy in women with preexisting cardiomyopathies and de novo HF, risk assessment and preconception planning, decisions about contraception, the safety of HF medications and implantable cardioverter-defibrillators during pregnancy, pregnancy in women with left ventricular assist devices and following heart transplantation.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008223DOI Listing
May 2021

Clinical Utility of SPECT in the Heart Transplant Population: Analysis from a Single Large-Volume Center.

Transplantation 2021 Apr 21. Epub 2021 Apr 21.

Departments of Imaging and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA Department of Cardiac Sciences, University of Calgary, Calgary AB, Canada.

Background: Survival after heart transplant has greatly improved, with median survival now over 12 years. Cardiac allograft vasculopathy (CAV), has become a major source of long-term morbidity and mortality. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is used for CAV surveillance, but there is limited data on its prognostic utility.

Methods: We retrospectively identified patients undergoing SPECT MPI for CAV surveillance at a single, large-volume center. Images were assessed with semi-quantitative visual scoring (summed stress score [SSS] and summed rest score [SRS]) and quantitatively with total perfusion defect (TPD).

Results: We studied 503 patients (mean age 62.5, 69.3% male) at a median of 9.0 years post-transplant. During mean follow-up of 5.1 ± 2.5 years, 114 (22.6%) patients died. The diagnostic accuracy for significant CAV (ISHLT grade 2 or 3) was highest for SSS with an area under the curve (AUC) of 0.650 and stress TPD (AUC 0.648), with no significant difference between SSS and stress TPD (p=0.061). Stress TPD (adjusted hazard ratio 1.07, p=0.018) was independently associated with all-cause mortality, while SSS was not (p=0.064). The prognostic accuracy of quantitative assessment of perfusion tended to be higher compared to semi-quantitative assessment, with the highest accuracy for stress TPD (area under the receiver operating curve 0.584).

Conclusions: While SPECT MPI identified a cohort of higher risk patients, with quantitative analysis of perfusion demonstrating higher prognostic accuracy. However, the overall prognostic accuracy was modest and alternative non-invasive modalities may be more suitable for CAV surveillance.
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http://dx.doi.org/10.1097/TP.0000000000003791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528902PMC
April 2021

The challenge of heart transplantation in sensitized patients-carfilzomib and the importance of shared experience.

J Heart Lung Transplant 2021 07 1;40(7):604-606. Epub 2021 Apr 1.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

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http://dx.doi.org/10.1016/j.healun.2021.03.023DOI Listing
July 2021

Stay Safe.

Ann Intern Med 2021 04;174(4):566

Cedars Sinai, Los Angeles, California.

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http://dx.doi.org/10.7326/M20-1275DOI Listing
April 2021

The Universal Definition of Heart Failure: Strengths and Opportunities.

J Card Fail 2021 06 10;27(6):622-624. Epub 2021 Apr 10.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai, Los Angeles, California.

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http://dx.doi.org/10.1016/j.cardfail.2021.03.009DOI Listing
June 2021

Heart transplant in Jehovah's Witness patients: A case-control study.

J Heart Lung Transplant 2021 07 21;40(7):575-579. Epub 2021 Mar 21.

Cedars-Sinai Medical Center, the Department of Cardiology, Smidt Heart Institute, Cedars-Sinai, Los Angeles, California. Electronic address:

Heart transplantation (HTx) improves quality of life and survival in patients with advanced heart failure. Jehovah's Witnesses (JW) patients decline blood transfusion (including red cells, plasma and platelets) and are prohibited from heart transplantation at many centers. We report our experience with 20 consecutive JW patients with advanced heart failure who declined blood products referred to our center for HTx consideration. Of these, 7 were declined for transplant due to prior sternotomy, need for multi-organ transplant, or being too well. Of 13 JW patients accepted for heart transplant listing, 8 underwent HTx at our center. Compared to non-JW controls without prior cardiac surgery matched for age and listing status, JW HTx recipients had comparable incidence of primary graft dysfunction, rejection, allograft vasculopathy, and survival and hemoglobin up to 1 year. With appropriate selection, patients who are JW and decline blood products may successfully undergo heart transplantation.
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http://dx.doi.org/10.1016/j.healun.2021.03.014DOI Listing
July 2021

Intermediate-term outcomes of heart transplantation for cardiac amyloidosis in the current era.

Clin Transplant 2021 06 19;35(6):e14308. Epub 2021 Apr 19.

Smidt Cedars-Sinai Heart Institute, Los Angeles, CA, USA.

Background: Cardiac amyloidosis (CA) has been historically noted with poor outcomes after heart transplant (HTx). However, strict patient selection, appropriate multi-organ transplant, and aggressive post-transplant therapy can result in favorable outcomes. We present the experience in the largest single-center cohort of CA patients post-HTx in the recent era.

Methods: Between January 2010 and December 2018, 51 CA patients underwent HTx-13 light-chain amyloidosis (AL) and 38 transthyretin amyloidosis (ATTR), 49 were included. Endpoints included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), and freedom from non-fatal major adverse cardiac events (NF-MACE).

Results: Overall 3-year survival was 81.6% (69.2% for AL and 86% for ATTR) and was comparable to survival for patients transplanted for non-amyloid restrictive cardiomyopathy (RCM) in the same period (89%, p = .46). Three-year freedom from CAV (84% vs. 89%, p = .98), NF-MACE (82% vs. 83%, p = .96), and any-treated rejection (95% vs. 89%, p = .54) were also comparable in both groups. No recurrence in amyloid was noted in endomyocardial biopsies. Six patients (46%) with AL amyloidosis underwent autologous stem cell transplant 1-year post-HTx, and two patients (8%) with variant ATTR-CA underwent combined heart-liver transplant due to cardiac cirrhosis.

Conclusion: In the current era, both AL and ATTR cardiac amyloidosis patients have acceptable outcomes after heart transplantation.
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http://dx.doi.org/10.1111/ctr.14308DOI Listing
June 2021
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