Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk

Shah, Sonia; Segar, Matthew W.; Kondamudi, Nitin; Ayers, Colby; Chandra, Alvin; Matulevicius, Susan; Agusala, Kartik; Peshock, Ronald M; Abbara, Suhny; Michos, Erin D.; Drazner, Mark H.; Lima, João A.C.; Longstreth, W. T.; Pandey, Ambarish

doi:10.1016/j.jchf.2022.05.007

JACC: Heart Failure

2022

DOI: 10.1016/j.jchf.2022.05.007

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Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk

Sonia Shah¹,

Matthew W. Segar²,

Nitin Kondamudi³

et al.

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Cited by 36 publications

(25 citation statements)

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“…The U‐shaped relationship between mortality and LVEF, with LVEF of 60–65% at the nadir of the curve, also suggests that patients with preserved LVEF should not be considered as a single entity 1,4 . Further indirect evidence comes from the results of the EMPEROR‐Preserved trial, where a lower benefit of empagliflozin was demonstrated in the subgroup with snLVEF 5 …”

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confidence: 99%

“…When thinking about ‘classical’ and recognized clinical models of snLVEF, an expert physician may firstly consider mitral insufficiency, hypertrophic cardiomyopathy, amyloidosis, aortic stenosis with low gradient, hypertension (in older women), or high‐output states, or alternatively acute illness such as sepsis or severe anaemia 12 . However, the growing amount of evidence clearly shows, actually, that these diseases are not associated with, or at least do not represent the majority of, snLVEF phenotypes and snLVEF‐GRS 1,4,6 …”

mentioning

confidence: 99%

“…Recent investigation showed an interesting U‐curve existing between LVEF and coronary flow reserve, with a higher incidence of reduced coronary flow reserve in LVEF <55% and in snLVEF patients compared to patients with preserved LVEF, both related to poor prognosis in terms of major adverse cardiovascular events (MACE) 18 . Shah et al 4 . just published on higher risk of MACE detected also in a different large cohort of snLVEF outpatients without previous cardiovascular disease, particularly in those with a lower indexed stroke volume.…”

mentioning

confidence: 99%

“…The U-shaped relationship between mortality and LVEF, with LVEF of 60-65% at the nadir of the curve, also suggests that patients with preserved LVEF should not be considered as a single entity. 1,4 Further indirect evidence comes from the results of the EMPEROR-Preserved trial, where a lower benefit of empagliflozin was demonstrated in the subgroup with snLVEF. 5 Moreover, the increased risk of all-cause mortality of individuals with snLVEF, confirmed also after adjusting for age, sex, height, body mass index, and multiple comorbidities, was independent from HF diagnosis and comparable to patients with reduced LVEF.…”

mentioning

confidence: 99%

“…However, the growing amount of evidence clearly shows, actually, that these diseases are not associated with, or at least do not represent the majority of, snLVEF phenotypes and snLVEF-GRS. 1,4,6 Coming back to physiology, the mechanisms underlining snLVEF are still only superficially explored and clarified. Recent investigation showed an interesting U-curve existing between LVEF and coronary flow reserve, with a higher incidence of reduced coronary flow reserve in LVEF <55% and in snLVEF patients compared to patients with preserved LVEF, both related to poor prognosis in terms of major adverse cardiovascular events (MACE).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Heart failure with supra‐normal left ventricular ejection fraction: distinct polygenic bases of an unrecognized phenotype

Sinagra

Paldino

Ferro

2022

European J of Heart Fail

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Heart failure with supra‐normal left ventricular ejection fraction: distinct polygenic bases of an unrecognized phenotype

Sinagra

Paldino

Ferro

2022

European J of Heart Fail

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β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction

Palau,

de la Espriella,

Seller

et al. 2024

JAMA Cardiol

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ImportanceIncreasing the patient’s heart rate (HR) has emerged as a therapeutic option in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence is conflicting, and the profile of patients who benefit most from this strategy remains unclear.ObjectiveTo assess the association of β-blocker treatment withdrawal with changes in the percentage of predicted peak oxygen consumption (VO2) across indexed left ventricular diastolic (iLVEDV) and indexed left ventricular systolic volumes (iLVESV), and left ventricular ejection fraction (LVEF) in patients with HFpEF and chronotropic incompetence.Design, Setting, and ParticipantsThis post hoc analysis was conducted using data from the investigator-blinded multicenter, randomized, and crossover clinical trial, PRESERVE-HR, that took place from October 1, 2018, through December 31, 2020, to investigate the short-term effects (2 weeks) of β-blocker withdrawal on peak oxygen consumption (peak VO2). Patients with stable HFpEF (New York Heart Association functional class II to III) receiving treatment with β-blocker and chronotropic incompetence were included.InterventionParticipants in the PRESERVE-HR trial were randomized to withdraw vs continue with β-blocker treatment. After 2 weeks, they were crossed over to receive the opposite intervention. This crossover randomized clinical trial examined the short-term effect of β-blocker withdrawal on peak VO2.Main Outcomes and MeasuresThe primary outcome was to evaluate the association between β-blocker withdrawal and short-term changes in percentage of peak VO2 across iLVEDV, iLVESV, and LVEF in patients with HFpEF and chronotropic incompetence treated with β-blocker.ResultsA total of 52 patients (mean age, 73 [SD, 13] years; 60% female) were randomized. The mean resting HR, peak HR, peak VO2, and percentage of peak VO2 were 65 (SD, 9) beats per minute (bpm), 97 (SD, 15) bpm, 12.4 (SD, 2.9) mL/kg per minute, and 72.4% (SD, 17.7%), respectively. The medians (minimum-maximum) of iLVEDV, iLVESV, and LVEF were 44 mL/m2 (IQR, 19-82), 15 mL/m2 (IQR, 7-32), and 64% (IQR, 52%-78%), respectively. After stopping β-blocker treatment, the median increase in peak HR was plus 30 bpm (95% CI, 25-35; P &lt; .001). β-Blocker cessation was differentially associated with change of percentage of peak VO2 across the continuum of iLVESV (P for interaction = .02), indicating a greater benefit in those with lower iLVESV.Conclusions and RelevanceIn this study, results showed that in patients with HFpEF and chronotropic incompetence receiving treatment with β-blocker, lower iLVESV may identify those with a greater short-term improvement in maximal functional capacity after stopping β-blocker treatment. Further studies are warranted for further investigation.Trial RegistrationClinicalTrials.gov (NCT03871803)

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Heart failure: an update from the last years and a look at the near future

et al. 2022

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In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

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Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk

Cited by 36 publications

References 23 publications

Heart failure with supra‐normal left ventricular ejection fraction: distinct polygenic bases of an unrecognized phenotype

Heart failure with supra‐normal left ventricular ejection fraction: distinct polygenic bases of an unrecognized phenotype

β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction

Heart failure: an update from the last years and a look at the near future

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