B P6 C51 Heart Failure with Preserved and Mildly Reduced Ejection Fraction

Question 1

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:

Answer 1

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

Question 2

Specifically in those with higher LVEF, risk factors included:

Answer 2

Higher BMI
Atrial fibrillation
Smoking

Question 3

In contrast _____ were associated with higher risk of HFrEF

Answer 3

Male sex
Hypertension
Higher heart rate
Prior cardiovascular disease
Higher cholesterol level
LV hypertrophy
LBBB

Question 4

However, _____ was associated with a higher risk of HFpEF and HFmrEF whereas _____ were associated with higher risk of HFrEF

Answer 4

HFpEF and HFmrEF: Old age

HFrEF: male sex and prior myocardial infarction

Question 5

_____ 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.

Answer 5

Atrial fibrillation

Question 6

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

Answer 6

Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC)

Question 7

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

Answer 7

Sudden death

Question 8

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.

Answer 8

NonCV hospitalization: HFpEF

CV hospitalizations: HFrEF

Question 9

The diagnosis of HFpEF and HFmrEF relies on:

Answer 9

(1) Clinical diagnosis of HF
(2) Evidence of a preserved or only mildly reduced LVEF (LVEF >40%)

Question 10

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%.

Question 11

Noncardiac Etiologies That Can Mimic the HFpEF Syndrome

Answer 11

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

Question 12

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 _____.

Answer 12

(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)

Question 13

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:

Answer 13

(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

Question 14

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 _____.

Answer 14

H2FPEF score

HFA-PEFF score

Question 15

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: _____

Answer 15

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)

Question 16

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 _____

Answer 16

Pre-test assessment
Echocardiography and natriuretic peptide score;Functional testing
Final etiology

Question 17

Scoring system for HFA-PEFF score

Answer 17

5 points is diagnostic of HFpEF

<2 points excludes HFpEF

Question 18

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.

Answer 18

Atrial fibrillation
Pulmonary arterial hypertension
Primary RV failure
Acute pulmonary embolism
Chronic kidney disease

Question 19

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

Answer 19

Cardiac amyloidosis

Question 20

. 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.

Question 21

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

Question 22

____ 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

Answer 22

LA volume

LAVI - 34 mL/m2

Question 23

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

Answer 23

LA minimal volume or LA reservoir strain

Question 24

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.

Answer 24

Athlete’s heart, high output states (e.g., cirrhosis), and atrial fibrillation

Question 25

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.

Answer 25

> 40 mm Hg

Question 26

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

Answer 26

RV fractional area change (normal >35%)
Tricuspid annular plane systolic excursion (normal >1.6 cm)
RV s’ velocity (normal >10 cm/sec)

Question 27

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

Answer 27

> 0.18

Question 28

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.

Answer 28

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.

Question 29

The ___ is often reduced in HFpEF patients, especially in patients with CAD or infiltrative cardiomyopathy.

Answer 29

Reduced s ‘ velocity (a marker of longitudinal motion of the myocardium)

Question 30

A ____ is reflective of impaired LA contraction and/or reduced LV end-diastolic chamber compliance.

Answer 30

Reduced a’ velocity

Question 31

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.

Answer 31

Reduced absolute LV global longitudinal strain (GLS)

Question 32

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

Question 33

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 ____

Answer 33

Apical sparing pattern

Question 34

______ 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

Answer 34

LA reservoir strain

Question 35

____ 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.

Answer 35

LA conduit strain

LA booster strain

Question 36

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

Answer 36

Exercise echocardiography

Question 36

When LA strain indices are abnormal out of proportion to the extent of LV dysfunction, a ___ as a cause of HFpEF should be considered.

Answer 36

Primary LA myopathy

Question 37

CMR is the reference standard for assessment of cardiac structure and global systolic function given its high temporal resolution.

Question 38

Furthermore, ___ provides assessment of myocardial scar, which may be due to myocardial infarction, myocarditis, or spe- cific cardiomyopathies depending on its distribution.

Answer 38

Late gadolinium enhancement

Question 39

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

Answer 39

T1 mapping with quantitation of the extracellular volume content
>25%

Question 40

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.

Answer 40

T2* imaging

Question 41

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.

Answer 41

Cardiac catheterization

Question 42

In general, pressure measurements should be made at ____ during normal, free breathing without asking the patient to perform breath hold maneuvers

Answer 42

End-expiration

Question 43

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.

Answer 43

Sinus - mid-A wave or at the base of the A wave
AF - base of the V wave

Question 44

____ in the RA pressure tracing are indicative of preserved RA contractile function and a stiff RV.

Answer 44

Tall A waves

Question 45

_____ in the RA pressure tracing can be seen in severe tricuspid regurgitation or in the presence of a stiff RA

Answer 45

Tall V waves

Question 46

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.

Answer 46

rapid X and Y descent

Question 47

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

Answer 47

Kussmaul’s sign

Question 48

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

Answer 48

High RV nadir pressure

Question 49

A ___ morphology of the RV pressure tracing can be seen in restrictive cardiomyopathy or constrictive pericarditis.

Answer 49

Dip- and-plateau (square root sign)

Question 50

Patients with HFpEF and HFmrEF often have elevated PA pressures, which is most commonly due to ___

Answer 50

Pulmonary venous hypertension

Question 51

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

Answer 51

DPG >5 to 7 mm Hg elev (PVR + pulmonary arteriopathy and venopathy)

Question 52

By definition, PCWP should be elevated at rest (____) or with passive leg raise or exercise (____) in patients with HFpEF and HFmrEF

Answer 52

Rest - 15 mm Hg
Exercise -25 mm Hg

Question 53

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

Answer 53

Stiff LA

Question 54

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.

Answer 54

PCWP

Question 55

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

Answer 55

Low stroke volume

Question 56

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.

Question 57

____ 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.

Answer 57

V waves - exaggerated

Question 58

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

Answer 58

PVH - parallel rise (mean PA, PCWP, CO)

Question 59

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 _____

Answer 59

HFpEF

Pulmonary vascular disease

Constrictive pericarditis, RV failure, or LA dysfunction

Question 60

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.

Answer 60

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

Question 61

Coronary vasodilator testing with assessment of ____ and ____ are also helpful in determining whether or not coronary microvascular dysfunction are present.

Answer 61

Coronary flow reserve (CFR) and the index of microvascular resistance (IMR)

Question 62

_____ 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

Answer 62

CFR

Question 63

The cutoff for defining coronary microvascular dysfunction varies by type of study but is generally defined as ____

Answer 63

CFR <2.0 to 2.5.

Question 64

A reduced CFR can be due to intrinsic coronary microvascular dysfunction but can also be present in patients with

Answer 64

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

Question 65

____, 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.

Answer 65

IMR index of microvascular resistance

Question 66

An IMR is abnormal and indicative of coronary microvascular dysfunction

Answer 66

IMR >/=23

Question 67

The combination of a ____ is most specific for coronary microvascular dysfunction and has been associated with a poor prognosis in HFpEF patients.

Answer 67

Reduced CFR and elevated IMR

Question 68

___ is the reference standard test for assessment of exercise intolerance and dyspnea

Answer 68

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

Question 69

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

Question 70

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.

Question 71

___ 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.

Answer 71

Nonalcoholic fatty liver disease (NAFLD) i

Question 72

Increased visceral adiposity is a major contributor to HFpEF pathophysiology and is not always apparent by simply examining the BMI in HFpEF patients.7

Question 73

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.

Question 74

From a hemodynamic perspective, the cardinal abnormality in HFpEF patients is ____.

Patients with HFpEF have marked elevation in PCWP with minimal exertion

Answer 74

LV end-diastolic pressure elevation (with resultant LA pressure elevation) at rest or with exertion

Question 75

____ 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

Answer 75

Systemic and coronary endothelial dysfunction

Question 76

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.

Answer 76

Diuretics

Question 77

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.

Answer 77

PEP-CHF trial

Question 78

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%

Answer 78

CHARM-Preserved

I-PRESERVE

Question 79

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

Answer 79

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%.

Question 80

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).

Answer 80

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%.

Question 81

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)

Answer 81

TOPCAT (Spironolactone for Heart Failure with Preserved Ejection Fraction)

Question 82

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

Answer 82

PARAGON HF trial (Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction)

Question 83

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.

Answer 83

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

Question 84

The ___ is an implantable hemodynamic monitor that is inserted into a pulmonary artery and transmits pulmonary pressures to health- care providers.

Answer 84

CardioMEMS heart sensor

Question 87

As with HFrEF, ___ may be useful in HFpEF, especially in patients with evidence of fluid overload.

Answer 87

Sodium and fluid restriction

Question 88

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.

Answer 88

Exercise-based interventions

Question 89

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.

Answer 89

LVEF <57%

Question 90

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

Answer 90

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.

Question 91

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

Answer 91

DELIVER HF (Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction)