Best of heart failure

19 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 459 the management of decompensated congestive heart failure. Dobutamine was associated with arrhythmia and tachycardia, whereas nesiritide reduced ventricular ectopy and did not increase heart rate suggesting a safer profile of nesiritide over dobutamine [ 144 ]. The 30-day mortality from pooled data from seven clini- cal trials (Table 24.2 ) [ 142 , 144 – 148 ] was 5.3% for Natrecor and 4.3% for control (hazard ratio 1.27 [0.81–2.01]). In a recent pooled analysis of three randomized studies [ 149 ], 485 patients were randomized to nesiritide and 377 to con- trol therapy. Death at 30 days occurred more frequently in patients treated with nesiritide than placebo at 30 days of follow-up (7.2% versus 4%, p = 0.059). 24.4.14 Mechanical Support of the Failing Heart The Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial [ 150 , 151 ] randomized 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device ( n = 68) or optimal medical management ( n = 61). Survival (52% versus 25%, p = 0.002) and quality of life were significantly improved with the device compared to medical therapy at 1 year. Serious adverse events did occur in the group when compared to medical therapy and included infection, bleeding, and device malfunction. In this trial, patients undergoing inotropic sup- port derived major mortality and quality of life benefits from the assist device compared to patients receiving medical therapy. Also, patients not undergoing inotropic support had an overall better survival rates both with and without the assist device, but differences did not reach significance. Recent improvements in the HeartMate VE left ventricu- lar assist device (LVAD) to the HeartMate XVE LVAD have recently led to significant improvements in outcomes [ 152 ] indicating that as technology and experience with LVAD evolve this therapy might become more accessible to the Class IV heart failure patient who is ineligible for cardiac transplantation. 24.5 Case Studies 24.5.1 Case Study 1 P.S. is a 57-year-old male with history of old myocardial infarction, ischemic cardiomyopathy, and an ejection frac- tion of 32%. He has been short of breath with minimal home activity, placing him in a Class III New York Heart Classification for failure. Patient has been on carvedilol 25 mg PO BID, lisinopril 20 mg PO daily, furosemide 60 mg PO daily, and spironolactone 25 mg PO BID. Patient is euvolemic on his current medical regimen. His electrocar- diogram showed a normal sinus rhythm with a left bundle branch block and a QRS complex duration of 140 ms. Patient was referred for biventricular pacing defibrillator placement. Two weeks post-procedure, the patient’s symptoms improved, and he was in Class II NYHC. Lisinopril was then discontinued, and 36 h after, he was started on sacubitril/val- sartan 24 mg/26 mg PO BID for 2 weeks. This was well tol- erated, and in 2 weeks ARNI dose was increased to 97 mg/103 mg PO BID. 24.5.2 Case Study 2 M.S. is a 35-year-old female with a recent viral infection and subsequent congestive heart failure. Echocardiography showed an ejection fraction of 25% and no evidence of sig- nificant valvular disease. Blood testing showed normal thy- roid function tests, negative antinuclear antibody, normal iron and iron saturation, normal liver function tests, and elec- trolytes. Computed tomography of the coronaries showed a calcium score of 0 and normal coronaries in a right dominant system. Patient was started on carvedilol 3.125 mg PO BID and titrated to 25 mg PO BID over a period of 2 months. She was also started on lisinopril 5 mg PO daily and increased to 20 g PO QD. After 6 months, patient’s ejection fraction Table 24.2 Percent 30-day mortality in seven nesiritide trials Trial Natrecor (%) Control (%) Hazard ratio Confidence interval Mills et al. 2.70 7.50 0.38 (0.05–2.67) PRECEDENT 3.70 6.10 0.6 (0.18–1.97) Efficacy 5.90 5.80 1.25 (0.24–6.45) Comparative 6.90 4.90 1.43 (0.53–3.97) VMAC 8.10 5.10 1.56 (0.75–3.24) PROACTION 4.2 0.90 4.99 (0.58–42.73) FUSION I 1.40 2.90 0.49 (0.07–3.47) Pooled (all) 5.30 4.30 1.27 (0.81–2.01) 24 Evidence-Based Management of the Patient with Congestive Heart Failure