Best of heart failure

13 been hospitalized with heart failure in the past 12 months. Ivabradine significantly reduced the relative risk of hospital- ization for worsening HF or CV death (RRR 18%, p < 0.0001); the significance is driven mostly by a reduction of rehospitalization. HFNEF describes a heterogeneous pool of patients that make about 50% of HF patients with a unique set of patho- physiologic mechanisms. These patients are typically older with hypertension, obesity, renal failure, anemia, and atrial fibrillation and are more likely to be females. There is also a high incidence of diabetes and coronary artery disease in these patients [ 7 ]. In contrast to patients with impaired left ventricular EF, HFNEF patients have non-dilated left ven- tricular cavity size, concentric instead of eccentric left ven- tricular hypertrophy, and a normal EF [ 34 ]. It is controversial whether LV systolic function is truly normal in patients with HFNEF because EF is an imprecise measure of left ventricular systolic function. However, inva- sive conductance studies suggested from pressure–volume loops that end-systolic pressure–volume relationship is steeper or normal in HFNEF suggesting a normal systolic function. On the other hand, end-diastolic pressure–volume relationship is shifted leftward and upward indicating dia- stolic dysfunction [ 35 , 36 ]. Diastolic dysfunction is not uncommon among elderly patients estimated at about 5.6%, but only 1% has HFNEF [ 37 ]. In one study, the product of left ventricular mass index and left atrial volume has the highest predictive accuracy for HFNEF [ 38 ]. In addition to ventricular stiffness, arterial stiffness has also been suggested to contribute to HFNEF, and the combined ventricular–arterial stiffness leads to an exaggerated hypertensive response after small increases in LV end-diastolic volume [ 7 ]. 24.3 ACC/AHA Classification of Congestive Heart Failure The current ACC/AHA classification for CHF [ 3 ] is comple- mentary to the New York Heart Classification (NYHC) [ 39 ] and helps define the evolution of symptoms of patients with CHF. In addition, the ACC/AHA classification focuses on the risk factors for CHF by identifying patients who have risk factors for CHF. This classification includes four stages of CHF: Stage A: Asymptomatic patients with no left ventricular dys- function but are at risk of developing CHF including patients with coronary artery disease, hypertension, dia- betes mellitus, family history of cardiomyopathy, and the metabolic syndrome. Stage A is not represented in the NYHC. Stage B : Asymptomatic patients with left ventricular dys- function. This is equivalent to Class I of the NYHC. Stage C : Symptom ventricular dysf Class II and Clas ple in the United Stage D : Symptom Class IV of the in the United Sta 24.4 Pharma Heart Fa 24.4.1 Heart Fai Fraction Dysfunct As noted above, o nisms of HFNEF is with diastolic dysf patients with HF a HFNEF. “True” H nary artery disease, strictive cardiomyo and right-sided fail mia, thyrotoxicosis carditis, or intracar Diastolic dysfun ditions including cor lar disease, age [ 4 secondary to intrace [ 42 ], and hypertrop ARB (losartan) has but did not change l Isolated diastolic identified in 11.5% ease with the use o atrial size and N-t (NT-proBNP) appe function [ 45 ]. Also, are seen with differe Recently an algo posed by the work Cardiology [ 47 ]. In toms of HF, normal with evidence of a distensibility, and d of HFNEF if one of PCWP > 12 mmHg ing, E/E ′ > 15 by ti DopplerwithaBNP mL or BNP > 200 and LVH or atrial mal pulmonary ven 24 Evidence-Based Management of the Patient with Congestive Heart Failure 453 reduction in mortality during an average follow-up of 20 months [ 73 ]. Echocardiography or isotope ventriculography has been used for periodic follow-up of patients with asympt matic left ventricular dysfunction. Patients with familial cardiomy- opathy need to have their immediate family me bers screened for asymptomatic left ventricular dysfunction [ 74 ]. 24.4.3 Symptomatic Left Ventricular Systolic Dysfunction Symptomatic left ventricular systolic dysfunction (Stage C, ACC/AHA classification) requires close follow-up and intense pharmacologic treatment (Table 24.1 ). In addition to risk factor modifications, patients will need to be treated with pharmacologic and mechanical means to improve their morbidity and mortality. Seri l monitoring of ejection frac- tion is also important. A summary of therapies for Stage C CHF is presented below. 24.4.4 Angiotensin-Converting Enzyme I hibitors (ACEI) ACEIs reduce mortality by 15–20% and reho pitalizations by 30–35% in patients with left ventricular sy tolic dysfunc- tion (ejection fraction of <40%). The Cooperative North Scandinavian Enalapril Survival Stu y (CONSENSUS) compared the effects of enalapril versus placebo o mortality in patients with severe CH . Enalapril reduced mortality by 31% at 1 year ( p = 0.001) a well as congestive heart failure hospitalizat on [ 75 ]. Th SOLVD tri l also confirmed the same findings. Patients receiving conventional treatment f r Class II an III heart failu e wer randomly assig ed to rec ive either plac bo ( n = 1284) or enalapril ( n = 1285). E alapril reduced mortality by 16% ( p = 0.0036) and co - gestiv heart failure by 26% ( p < 0.0001) at an average fol- low-up o 41.4 months [ 76 ]. Furthermore, SOLVD showed that enalapril attenuates progressive increases in left ventric- ular dilatation and hypertrophy in p tients with educed left ventricular function [ 77 ]. Finall , Pitt nd colleagues lso has shown that enalapril reduced development of heart fa l- ure by 37% and ospitalization from heart failure by 36% ( p < 0.001) [ 78 ]. ACEI post-MI has als shown a significant mortality benefit. Th A te Infarction Ramipril Efficacy (AIRE) study [ 79 ] howed a 27% ( p = 0.002) reduction in the 30-month cu ulative mortality with ramipril over placebo in post-MI CHF patients. Also, in the Survival an Ventricular Enlargement (SAVE) trial [ 80 ], captopril was administered 3–16 d ys after myocardial infarction in patients with asymptomatic left ventricular dysfunction (EF < 40%) and followed for an average of 42 months. Captopril improved survival (risk redu tion was 19%, p = 0.019) and morbidity. In addition, in the Trandolapr l Cardiac Evaluation (TRACE) study, trandolapril reduc d mortality by 22% ( p = 0.01) n patients with reduced left vent icular function af er an MI. Trand lapril reduced overall mortality, mortality from cardiovascular causes, sudden death, an the development of severe heart failure [ 81 ]. Finally, in the Survival of Myocardial Infarc ion Long-Term Ev luation (SMILE) study [ 82 ], zofenopril reduced the risk of death or severe congestive heart failure by 34% ( p = 0.018) at 6 we ks when in tiate early after MI. At 1 year, the redu tion in mor ality risk was 29% ( p = 0.011). Early initiation of ACEI in hospital leads to a higher use of ACEI on an outpatient basis, and, therefore, initiating ACEI early is mpor ant in all patients with HF. Table 24.1 Commonly used drugs in the treatment of congestive heart failure Angiotensin-converting enzyme inhibitors Accupril 5–40 mg PO QD, max 40 mg/day, start 5–10 mg PO QD Captopril 12.5–50 mg PO TID, max 150 mg/day, start 6.25– 12.5 mg PO TID Enalapril 2.5–20 mg PO BID, max 40 mg/day, start at 2.5 mg QD Lisinopril 5–20 mg PO QD, max 40 mg/day, start 2.5–5 mg PO QD Monopril 10–40 mg PO QD/BID, max 80 mg/day, start 10 mg PO QD Perindopril 4–16 mg PO QD, max 16 mg/day, start 2 mg PO QD Ramipril 5 mg PO BID, max 10 mg/day, start at 2.5 mg PO BID Angiotensin receptor blockers Losartan 25–100 mg PO QD, max 100 mg/day, start 25–50 mg PO QD a Candesartan 8–32 mg PO QD, max 32 mg/day, start 16 mg PO QD a Valsartan 40–160 mg PO BID, max 320 mg/day, start 40 mg PO BID Irbesartan 75–300 mg PO QD, max 300 mg/day, start 75 mg PO QD a Beta blockers Carvedilol 3.125–25 mg PO BID, max 50 mg PO QD, start 3.125 mg PO BID Metoprolol succinate 12.5–200 mg PO QD, max 200 mg/day, start 12.5 mg PO QD Bisoprolol 5–10 mg PO QD, max 10 mg PO QD, start 2.5 mg PO QD a Aldosterone antagonists Spironolactone 12.5–25 mg PO BID, max 50 mg/day, start 12.5 mg PO BID Eplerenone 50 mg PO QD, max 50 mg/day, start 25 mg PO QD b Angiotension receptor neprilysin inhibitor (ARNI) Sacubitril/valsartan 24 mg sacubitril/26 mg valsartan PO BID to be increased to 49 mg/51 mg PO BID and 97 mg/103 mg PO BID as tolerated every 2 weeks c HCN channel blocker Ivabradine 5 mg PO BID. Can increase to maximum dose of 7.5 mg PO BD a Off-label use b For CHF patients post-myocardial infarction c Sacubitril/valsartan should not be used with ACEI 24 Evidence-Based Management of the Patient with Congestive Heart Failure