B P6 C51 Heart Failure with Preserved and Mildly Reduced Ejection Fraction Flashcards
In the Framingham Heart Study (FHS), an examination of predictors of 8-year risk of HF patients with LVEF >45% versus those with LVEF </=45% showed that predictors of all incident HF included:
Older age
Male sex
Hypertension
Higher body mass index (BMI)
Increasing heart rate
Coronary artery disease (CAD)
Diabetes mellitus
Smoking
Valve disease
Lower HDL cholesterol
Atrial fibrillation
LV hypertrophy or LBBB
Specifically in those with higher LVEF, risk factors included:
Higher BMI
Atrial fibrillation
Smoking
In contrast _____ were associated with higher risk of HFrEF
Male sex
Hypertension
Higher heart rate
Prior cardiovascular disease
Higher cholesterol level
LV hypertrophy
LBBB
However, _____ was associated with a higher risk of HFpEF and HFmrEF whereas _____ were associated with higher risk of HFrEF
HFpEF and HFmrEF: Old age
HFrEF: male sex and prior myocardial infarction
_____ is the most common arrhythmia in patients with HFpEF and HFmrEF, with a prevalence of 20% to 40% at the time of presentation, and occurring in two-thirds of these patients at some point during their course.
Atrial fibrillation
The _____ meta-analysis inclusive of data from clinical trials, reported that patients with HFpEF had lower risk of death from any cause compared with those with HFrEF independent of age, sex, and etiology.31 The death rate was 12.1 (95% CI: 11.7, 12.6) per 100 patient-years in HFpEF and 14.1 (95% CI: 13.8, 14.4) per 100 patient-years in HFrEF, with an adjusted hazard ratio (HR) of 0.68 (95% CI: 0.64, 0.71) for HFpEF versus HFrEF; death rates were lower in randomized trials alone,and the lower risk in HFpEF than HFrEF was more prominent in ambulatory versus hospitalized patients.3
Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC)
Among cardiovascular causes of death, _____accounted for up to 43% of cardiovascular mortality (“25% to 30% of total deaths) in clinical trials that included patients with HF and LVEF >40%, with HF deaths accounting for another 20% to 30% of cardiovascular deaths
Sudden death
Although total hospitalization rates were similar across the spectrum of LVEF, noncardiovascular hospitalizations were higher in those with _____, whereas cardiovascular hospitalizations were lower, when compared with HFrEF.
NonCV hospitalization: HFpEF
CV hospitalizations: HFrEF
The diagnosis of HFpEF and HFmrEF relies on:
(1) Clinical diagnosis of HF
(2) Evidence of a preserved or only mildly reduced LVEF (LVEF >40%)
The specific LVEF cutoff for HFpEF has been debated and has been different in different contexts, with recent guidelines suggesting that HFpEF should be defined as LVEF 50% and HFmrEF defined as LVEF between 40% and 49%.
Noncardiac Etiologies That Can Mimic the HFpEF Syndrome
Obesity
Chronic lung disease
Chronic kidney disease with minimal cardiac structural or functional abnormalities
Primary cirrhosis
Extrinsic compression of the LA, LV, or IVC
IVC obstruction
Lymphedema
Anemia
However, the diagnosis can be challenging in patients with dyspnea and exercise intolerance who do not have overt signs of elevated filling pressures and natriuretic peptide levels below typical thresholds used to make the diagnosis of HF, which occurs commonly in some patients (up to 30% to 40%, especially in patients who are obese). In these patients, provocative testing (e.g., exercise) can be useful to make the diagnosis by _____.
(1) Echocardiography (elevated E/e% ratio at peak exercise)
OR
(2) Invasive hemodynamic testing (PCWP 25 mm Hg with passive leg raise or during exercise)
Echocardiographic evidence of LV diastolic dysfunction is chal- lenging and should not be used as the sole criteria for the diagnosis of HFpEF for several reasons:
(1) diastolic function on echocardiography may be uninterpretable, equivocal, or misinterpreted;
(2) many older patients without the HF syndrome have evidence of diastolic dysfunction;
(3) while echocardiography is useful for the diagnosis of impaired relaxation, E/e’ ratio (an estimate of LV filling pressures) is often in the indeterminate range (8 to 15), and echocardiography has not proven useful for the assessment of LV chamber compliance in the clinical setting
Two scoring systems have been developed to assist in the diagnosis of HFpEF in patients with dyspnea in whom the diagnosis is in question: the _____.
H2FPEF score
HFA-PEFF score
The H2FPEF score was systematically derived and validated at a single center (Mayo Clinic, Rochester, MN). HFpEF was diagnosed in patients with PCWP >/=15 mm Hg at rest or >/=25 mm Hg during exercise. The final diagnostic model included the following weighted components: _____
BMI >30 g/m2 (2 points)
2 or more antihypertensive medications (1 point)
Atrial fibrillation (3 points)
Echocardiographic PASP >35 mm Hg (1point)
Age >60 years (1 point)
Echocardiographic E/e’ >9 (1 point)
The HFA-PEFF score was developed by a group of experts convened by the European Society of Cardiology Heart Failure Association. The “PEFF” mnemonic stands for _____
Pre-test assessment
Echocardiography and natriuretic peptide score;Functional testing
Final etiology
Scoring system for HFA-PEFF score
5 points is diagnostic of HFpEF
<2 points excludes HFpEF
Although an elevated NP level can be helpful to diagnose HF in patients with LVEF >40%, other causes of elevated NP levels such as _____ must be considered in the differential diagnosis.
Atrial fibrillation
Pulmonary arterial hypertension
Primary RV failure
Acute pulmonary embolism
Chronic kidney disease
High-sensitivity troponin (hsTnT) is also useful in the evaluation of patients with HFpEF and HFmrEF, and elevation in hsTnT can signify a more “myocardial” phenotype of HFpEF, can alert the clinician to the potential presence of an infiltrative cardiomyopathy such as _____, and may reflect impaired subendocardial perfusion due to coronary microvascular dysfunction, particularly if measured during or immediately after exercise testing
Cardiac amyloidosis
. Although not all patients with HFpEF or HFmrEF have LV hypertrophy, the majority have concentric LV remodeling, defined by a relative wall thickness (2 × posterior wall thickness/LV end-diastolic dimension) >0.42.
Assessment of LV mass index in relation to relative wall thickness can also be helpful because it can be used to categorize LV geometry (normal, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy), which can provide clues to the etiology
____ is also very useful for the diagnosis because it pro- vides insight into chronic LA pressure overload.
Although maximal LA volume index to body surface area ___ is the guideline-based cutoff for LA enlargement, it can be challenging to use because of the high prevalence of obesity in these patients, which results in lower values. For these reasons, it is important to examine the LA in relation to the other chambers of the heart
LA volume
LAVI - 34 mL/m2
An LA that is as large or larger than the LV implies that the LA is not emptying properly to adequately fill the LV, which is common in HFpEF.
Therefore, ___ may be better tools to help diagnose and manage these patients
LA minimal volume or LA reservoir strain
It is important to note that other conditions can result in LV hypertrophy and/or LA enlargement in the setting of a preserved LVEF.
These include ____, underscoring the importance of comprehensive echocardiographic assessment in these patients.
Athlete’s heart, high output states (e.g., cirrhosis), and atrial fibrillation
Conventional echocardiography is also useful for the assessment of load on the right heart in patients with HFpEF and HFmrEF.
Elevated pulmonary artery systolic pressure (____) especially when coupled with LA enlargement or dysfunction, is common in HFpEF, and this elevation is considered secondary to left sided heart disease.
> 40 mm Hg
As HFpEF worsens, RV enlargement and dysfunction often occur in response to chronic elevation in LA and pulmonary venous pressures. Thus, it is important to examine and quantify the right heart on echocardiography in all patients with HFpEF with indices such as
RV fractional area change (normal >35%)
Tricuspid annular plane systolic excursion (normal >1.6 cm)
RV s’ velocity (normal >10 cm/sec)
The ratio of tricuspid regurgitation velocity (in m/sec) to RV outflow tract velocity time integral (in cm) ___ is indicative of elevated total pulmonary resistance and should prompt evaluation of the possibility of pulmonary vascular disease
> 0.18
Tissue Doppler imaging (TDI) can be helpful in the assessment of patients with suspected HFpEF or HFmrEF.
The ___ is a marker of LV relaxation and is usually reduced in patients with heart failure regardless of LVEF.
Early diastolic (e’) velocity - reduced
Tissue Doppler imaging can be used to determine the extent of myocardial involvement in HFpEF.
Reductions in systolic (sʹ), early diastolic (eʹ), and late diastolic (aʹ) velocities, prolongation of isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT), and reduction in ejection time are all signs of a sick myocardium.
The ___ is often reduced in HFpEF patients, especially in patients with CAD or infiltrative cardiomyopathy.
Reduced s ‘ velocity (a marker of longitudinal motion of the myocardium)
A ____ is reflective of impaired LA contraction and/or reduced LV end-diastolic chamber compliance.
Reduced a’ velocity
Speckle-tracking echocardiography has emerged as an important diagnostic and prognostic tool in patients with HFpEF and HFmrEF and has provided insights into the pathophysiology.
Similar to s’ velocity, a _____ value is indicative of reduced longitudinal fiber LV function (a marker of LV subendocardial function, which is often affected by risk factors that lead to HFpEF) even in the setting of a preserved LVEF and is often present in patients with HFpEF.
Reduced absolute LV global longitudinal strain (GLS)
Although values of GLS can vary based on type of echocardi- ography machine and software used, an absolute GLS value of >18% is considered normal, 16% to 18% borderline, and <16% abnormal
Polar bullseye maps of the LV longitudinal strain pattern are also useful for determining the potential etiology of HFpEF (Fig. 51.4C) because it can help differentiate patients who have diffuse myocardial fibrosis from those who have cardiac amyloidosis, who would generally have an ____
Apical sparing pattern
______ is indicative of the ability of the LA to fill during ventricular systole; when reduced, it is associated with poor prognosis and reflects increased LA pressure and/or reduced compliance of the LA
LA reservoir strain
____ reflects the ability of the LA to empty properly during passive filling of the LV in early diastole, and ____ is indicative of the ability of the LA contractile function.
LA conduit strain
LA booster strain
Most compensated patients with HFpEF do not have symptoms at rest but become very symptomatic with exertion. Thus, ____ can be very useful in the evaluation of HFpEF patients
Exercise echocardiography
When LA strain indices are abnormal out of proportion to the extent of LV dysfunction, a ___ as a cause of HFpEF should be considered.
Primary LA myopathy
CMR is the reference standard for assessment of cardiac structure and global systolic function given its high temporal resolution.
Furthermore, ___ provides assessment of myocardial scar, which may be due to myocardial infarction, myocarditis, or spe- cific cardiomyopathies depending on its distribution.
Late gadolinium enhancement
However, some patients with HFpEF and HFmrEF have diffuse myocardial fibrosis which cannot be easily detected on conventional CMR imaging with contrast; instead, T1 mapping with quantitation of the extracellular volume content can be used and when elevated (typically ____) is indicative of either diffuse myocardial fibrosis or extracellular deposition of proteins as is seen in cardiac amyloidosis
T1 mapping with quantitation of the extracellular volume content
>25%
T2 mapping is also useful for the diagnosis of myocardial edema, which can be present in cases of myocarditis (eFig. 51.4B). In addition, ____ can be useful for the quantitation of myocardial iron content when the diagnosis of hemochromatosis is under consideration.
T2* imaging
In patients in whom noninvasive tests are equivocal and the diagnosis of HFpEF is in question, if there is need to differentiate between pulmonary arterial hypertension and HFpEF (i.e., pulmonary venous hypertension), or if there are questions about the physiology or volume status of a patient with known HFpEF, ____ remains the reference standard for assessment of invasive hemodynamics.
Cardiac catheterization
In general, pressure measurements should be made at ____ during normal, free breathing without asking the patient to perform breath hold maneuvers
End-expiration
Right atrial pressure and PCWP tracings should be measured ____ in patients in sinus rhythm and at the _____ in patients with atrial arrhythmias in the absence of A waves.
Sinus - mid-A wave or at the base of the A wave
AF - base of the V wave
____ in the RA pressure tracing are indicative of preserved RA contractile function and a stiff RV.
Tall A waves
_____ in the RA pressure tracing can be seen in severe tricuspid regurgitation or in the presence of a stiff RA
Tall V waves
A ____ can be seen in patients with the HFpEF clinical syndrome who have a restrictive cardiomyopathy (which can be isolated to the RV) or constrictive pericarditis.
rapid X and Y descent
A rise in RA pressure during inspiration (____) can be seen in patients with HFpEF who have a stiff RV, constrictive pericarditis, or significant tricuspid regurgitation
Kussmaul’s sign
A ____ can be indicative of significant volume overload, and an exaggerated A wave in the RV pressure tracing can be seen in patients with a stiff RV
High RV nadir pressure
A ___ morphology of the RV pressure tracing can be seen in restrictive cardiomyopathy or constrictive pericarditis.
Dip- and-plateau (square root sign)
Patients with HFpEF and HFmrEF often have elevated PA pressures, which is most commonly due to ___
Pulmonary venous hypertension
Elevated PVR (>3 Wood units) primarily due to PA systolic pressure elevation can be differentiated from PVR elevation due to concomitant pulmonary arteriopathy and venopathy by examining the diastolic pressure gradient (DPG; PA diastolic pressure minus PCWP) which will be elevated (____) in these cases
DPG >5 to 7 mm Hg elev (PVR + pulmonary arteriopathy and venopathy)
By definition, PCWP should be elevated at rest (____) or with passive leg raise or exercise (____) in patients with HFpEF and HFmrEF
Rest - 15 mm Hg
Exercise -25 mm Hg
Tall V waves in the PCWP tracing are also often seen either at rest, during exercise, or during intravenous fluid challenge in HFmrEF and HFpEF and typically reflects a ____ more commonly than severe mitral regurgitation
Stiff LA
PCWP is an integrated measure of the burden of LA stiffness (and indirectly the LV stiffness) on the pulmonary circulation, while the LVEDP only provides information on LV compliance.
This is the best measure to use for the calculation of PVR because poor LA compliance (with resultant accentuated LA pressure waves) is what the pulmonary circulation “sees” and what overloads it, not the LVEDP.
PCWP
Restrictive cardiomyopathy, LA failure due to atrial fibrillation or LA myopathy, valvular heart disease, pulmonary vascular disease, and RV failure are all potential causes of a ___ in the setting of elevated cardiac filling pressures
Low stroke volume
As mentioned earlier, exercise can be used in equivocal cases, and exercise invasive hemodynamic testing is considered to be the gold standard test for diagnosis.
____ in the PCWP tracing often become exaggerated during exercise because the LA is unable to handle the extra load that occurs due to splanchnic vasoconstriction leading to a large volume shift of blood from the splanchnic circulation and liver to the stiff left heart.
V waves - exaggerated
In patients with passive pulmonary venous hypertension, the mean PA pressure and PCWP will rise in ____ with increasing cardiac output during exercise whereas the mean PA pressure will rise more rapidly compared with PCWP in the setting of intrin- sic pulmonary vascular disease
PVH - parallel rise (mean PA, PCWP, CO)
A fluid challenge (10 cc/kg of warmed normal saline over a few minutes) can be safely administered to patients with HFpEF who have an RA pressure </=12 mm Hg.
Exaggerated rise in PCWP is indicative of ____
Exaggerated rise in PA pressure relative to PCWP is indicative of ____
Lack of augmentation (or reduced) cardiac output after fluid challenge can be seen in the setting of _____
HFpEF
Pulmonary vascular disease
Constrictive pericarditis, RV failure, or LA dysfunction
In patients with elevated PVR, administration of a systemic vasodilator such as ____ can be helpful to differentiate pulmonary venous hypertension from intrinsic pulmonary vascular disease.
If nitroprusside administration results in reduction in SVR, PCWP, and mean PA pressure, the pulmonary hypertension is likely due to _____.
However, if there is a reduction in SVR and PCWP and yet the mean PA pressure remains elevated (in which case the PVR and DPG will also remain elevated), intrinsic pulmonary vascular disease is likely present.
Intravenous nitroprusside
Reduction in SVR, PCWP, and mean PA pressure - Pulmonary venous hypertension
Reduction in SVR and PCWP and yet the mean PA pressure remains elevated (PVR and DPG will also remain elevated) - Intrinsic pulmonary vascular disease
Coronary vasodilator testing with assessment of ____ and ____ are also helpful in determining whether or not coronary microvascular dysfunction are present.
Coronary flow reserve (CFR) and the index of microvascular resistance (IMR)
_____ is defined as the ratio of hyperemic coronary flow (in response to adenosine, for example) to resting coronary flow, and can be measured using invasive coronary flow testing, positron emission tomography (PET), CMR, or transthoracic Doppler echocardiography
CFR
The cutoff for defining coronary microvascular dysfunction varies by type of study but is generally defined as ____
CFR <2.0 to 2.5.
A reduced CFR can be due to intrinsic coronary microvascular dysfunction but can also be present in patients with
Epicardial CAD
Extrinsic compression of the coronary microvasculature (e.g., due to interstitial myocardial fibrosis)
Coronary microvascular capillary rarefaction (due to severely diseased coronary microvasculature)
Elevated cardiac filling pressure
____, which is more specific to the coronary microvasculature, may be less susceptible to hemodynamic factors but currently can be measured only with invasive coronary flow techniques.
IMR index of microvascular resistance
An IMR is abnormal and indicative of coronary microvascular dysfunction
IMR >/=23
The combination of a ____ is most specific for coronary microvascular dysfunction and has been associated with a poor prognosis in HFpEF patients.
Reduced CFR and elevated IMR
___ is the reference standard test for assessment of exercise intolerance and dyspnea
Cardiopulmonary exercise testing (CPET)
Reduced peak oxygen consumption is reflective of inadequate augmentation of cardiac output and/or peripheral skeletal muscle extraction during exercise, both of which are frequently present in HFpEF
As in other chronic diseases, there is loss of skeletal muscle and increased intramuscular adiposity. Furthermore, there is a transition between type I to type II muscle fibers in HFpEF, which results in impaired exercise tolerance in HFpEF
Patients with HFpEF also have systemic microvascular dysfunction, which, when present in the skeletal muscles, results in decreased oxygen extraction, which has been shown to account for 50% of the reduction in peak VO2 in HFpEF patients.
___ is common in mor- bidly obese patients and is associated with worse LV longitudinal strain, diastolic dysfunction, and higher stroke volume in the general popula- tion, all of which can contribute to a HFpEF phenotype.
Nonalcoholic fatty liver disease (NAFLD) i
Increased visceral adiposity is a major contributor to HFpEF pathophysiology and is not always apparent by simply examining the BMI in HFpEF patients.7
Multiple methods for evaluating the presence and extent of visceral adiposity are available, including waist-hip circumference ratio, dual-energy X-ray absorptiom- etry (DEXA) scanning, and CT or MRI of the chest and abdomen. Several biomarkers, including increased triglyceride/HDL ratio, hyperglycemia with insulin resistance, increased plasminogen activator inhibitor-1 (PAI- 1), and reduced vitamin D levels are also indicative of increased visceral adiposity.
From a hemodynamic perspective, the cardinal abnormality in HFpEF patients is ____.
Patients with HFpEF have marked elevation in PCWP with minimal exertion
LV end-diastolic pressure elevation (with resultant LA pressure elevation) at rest or with exertion
____ are common in HFpEF. CFR is reduced in up to 75% of HFpEF patients,60 and evidence of coronary microvascular disease is present in the majority of HFpEF patients on autopsy
Systemic and coronary endothelial dysfunction
As in all patients with HF,those with HFpEF and HFmrEF typically have some degree of volume overload.Many will have evidence of elevated intracardiac filling pressures, both at rest and during exertion, which contributes to shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and right-sided symptoms such as lower extremity edema and early satiety.
Thus, decongestive therapy with ___ remains empiric cornerstone therapy for patients with HFpEF and HFmrEF.
Diuretics
The ACE inhibitor perindopril was compared with placebo in patients with HF and LVEF >45%
An 850-patient trial in which event rates were lower than expected and in which many patients withdrew from therapy after a year (with a high frequency of crossover to ACE inhibitor therapy in the placebo arm).
Overall, the hazard ratio for the primary endpoint,a composite of all-cause mortality and unplanned HF hospitalization, was 0.92 (95% CI 0.70 to 1.21), although at 1 year, before a substantial number of dropouts from the ACE inhibitor arm, there was nominal reduction in both the primary endpoint and HF hospitalization, as well as improvement in functional class and 6-minute walk test distance.
PEP-CHF trial
Two large outcomes trials with angiotensin receptor blockers have been performed in patients with HF and LVEF >40%:
____ which compared candesartan to placebo in patients with HF and LVEF >40%
____ which compared irbesartan to placebo in patients with HF and LVEF >45%
CHARM-Preserved
I-PRESERVE
Enrolled 3023 patients with HF and LVEF >40%, and the hazard ratio for the primary endpoint of time to first HF hospitalization or cardiovascular death was 0.89 (95% CI 0.77 to 1.03),P = 0.12.
This result was stronger in several prespecified and post hoc analyses, including an analysis adjusting for baseline covariates, and in analyses using total number of hospitalization events rather than time to first event.
There was no observed effect on mortality
CHARM-Preserved trial (Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction)
Candesartan has a moderate impact in preventing admissions for CHF among patients who have heart failure and LVEF higher than 40%.
Enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II, III, or IV heart failure and an ejection fraction of at least 45% and randomly assigned them to receive 300 mg of irbesartan or placebo per day. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke).
The primary outcome of all-cause death or cardiovascular hospitalization was similar between treatment groups (HR 0.95, 95% CI 0.86 to 1.05; P = 0.35).
Z I-PRESERVE (Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction)
The I-PRESERVE trisl did not show a benefit comparing irbesartan to placebo in patients with HF and an LVEF above 45%.
Compared spironolactone to placebo in 3445 patients with HFpEF. The entry criteria required signs and symptoms of HF with either elevation in natriuretic peptides or a history of HF hospitalization within the past year, and only patients with potassium <5.0 mmol/L, serum creatinine <2.5 mg/dL, and estimated glomerular filtra- tion rate 30 mL/min/1.73 m2 were included.
The primary endpoint of the trial was a composite of cardiovascular death, HF hospitalization or aborted cardiac arrest, and the overall results showed an 11% non- significant risk reduction (HR 0.89, 95% CI 0.77 to 1.04, P = 0.14).
Only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04)
TOPCAT (Spironolactone for Heart Failure with Preserved Ejection Fraction)
In a phase II trial in patients with HF and LVEF of 45% or greater, sacubitril/valsartan reduced NT-proBNP, a natriuretic peptide marker that is not directly affected by a neprilysin inhibitor, improved NYHA class, and reduced LA size compared with valsartan
Based on these findings, the ___ trial tested sacubitril/valsartan compared with valsartan in 4822 patients with NYHA Class II to IV HF, and LVEF 45%.108 In contrast to prior HFpEF trials, patients were required to have elevation in natriuretic peptides and evidence of structural heart disease.
Moreover, the primary endpoint of was a composite of cardiovascu- lar death and total (first and recurrent) HF hospitalizations utilizing a novel recurrent events analysis.
This showed a 13% reduction in total HF hospitalizations and cardiovascular death (rate ratio 0.87, 95% CI 0.75 to 1.01, P = 0.059), which just missed statistical significance
PARAGON HF trial (Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction)
In the ___ trial, the CardioMEMS sensor was tested in conjunction with a protocol-driven algorithm by which physicians utilized device information to make therapeutic changes.
Patients were randomized to either an algorithm-based strategy based on utilizing remote data from the device, or standard medical therapy.
Patients in the device-strategy arm demonstrated a significant decrease in pulmonary artery diastolic and systolic pressures, as well as a 52% decrease in HF-related events, an increase in days alive out of hospital and improvement in quality of life.
CHAMPION trial
The benefit observed was similar in patients across the spectrum of ejection fraction, suggesting that careful assessment of hemodynamic variables and appli- cation of therapeutic algorithms based on these assessments could improve outcomes in patients with HF regardless of ejection fraction
The ___ is an implantable hemodynamic monitor that is inserted into a pulmonary artery and transmits pulmonary pressures to health- care providers.
CardioMEMS heart sensor
As with HFrEF, ___ may be useful in HFpEF, especially in patients with evidence of fluid overload.
Sodium and fluid restriction
In contrast to most pharmacologic intervention trials for HFpEF, ____ have consistently demonstrated clinically meaningful improvements in objectively measured exercise capacity (peak oxygen uptake, total exercise time, and 6-minute walk distance), symptoms, and quality of life.
Exercise-based interventions
In a prespecified analysis, the PARAGON-HF trial also found significant therapeutic heterogeneity based on LVEF with patients in the lower end of the ejection fraction spectrum studied (LVEF _____) demonstrating greater benefit from sacubitril/valsartan compared with valsartan.
These data collectively suggest that HF patients with mildly reduced ejection fraction may benefit from therapies that benefit HFrEF patients, and this concept is reflected in the recent FDA approval for sacubitril/valsartan.
LVEF <57%
Randomly assigned 5988 patients with class II–IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.
Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes
EMPEROR PRESERVED trial (Empagliflozin in Heart Failure with a Preserved Ejection Fraction)
These results were driven by reduction in heart failure hospitalization and the benefit declined with increasing ejection fraction.
Randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death,
Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction
DELIVER HF (Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction)
