Coronary artery disease is present in approximately 50–70 % of patients with ADHF [7, 25–30]. Patients may present with ACS complicated by heart failure or ADHF with underlying CAD.

Approximately 10–20 % of patients with ACS have associated heart failure on presentation and another 10 % of ACS patients develop heart failure during hospitalization. Patients with ACS due to a STEMI typically have chest pain, diagnostic ECG changes and high levels of biomarkers consistent with substantial myocardial injury [29]. Patients with heart failure complicating an STEMI (either on presentation or developing later after hospitalization) have significantly increased in-hospital and post-discharge mortality compared to patients without heart failure [29–32]. Patients with ACS who develop heart failure after admission are at greater risk than patients with ACS who have heart failure on presentation [30, 32]. The severity of heart failure measured by the Killip classification is a powerful predictor of mortality in patients with heart failure complicating ACS. Patients with Killip class II or III are 4 times more likely to die during hospitalization compared with Killip class I patients while patients with Killip class IV (cardiogenic shock) are 10 times more likely [30, 32]. Patients with heart failure and unstable angina have also been found have a significant fourfold increase in mortality compared to similar patients without HF [31].

The Global Registry of Acute Coronary Events (GRACE) enrolled 16,166 patients with ACS. Patients who presented with HF complicating ACS had lower rates of catheterization and PCI and were less likely patients receive β-blockers and statins [31]. In the National Registry of Myocardial Infarction (NRMI), patients with HF complicating ACS were less likely to receive aspirin, heparin, intravenous nitroglycerine and β-blockers compared to patients with ACS without heart failure. In addition, patients with heart failure were less likely to undergo PCI or CABG compared with patients without heart failure on presentation (40 % vs 20 %) [32].

An analysis of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Outcomes with Early Implementation of the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines (CRUSADE) initiative (2.8 % of patients had HF) demonstrated that patients with a non-STEMI with heart failure with preserved EF had a significantly higher mortality rate than patients without HF and preserved systolic function and a similar mortality to patients with no HF and systolic dysfunction. Patients with both HF and systolic dysfunction had the highest mortality (1.5 % vs 5.7 % vs 5.8 % vs 10.7 %). Cardiac catheterization and PCI rates were lower for patients without heart failure with systolic dysfunction and with HF with or without systolic dysfunction. Patients with HF received aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitors, heparin, B-blockers and statins less frequently than patients with no HF and preserved systolic function [33].

There is broad consensus that patients with HF complicating ACS should undergo urgent coronary angiography and coronary intervention in the catheterization laboratory [1, 2, 9, 34, 35].

It has been estimated that 50–70 % of patients with ADHF have concomitant coronary artery disease. Registry data suggest that CAD is associated with higher in-hospital and post-discharge mortality rates. In the OPTIMIZE – Registry, in-hospital mortality rates were 3.75 % vs 2.9 % and post-discharge 60–90 day mortality rates were 9.2 vs 6.9 % in patients with CAD vs no CAD [36].

In multicenter registries of patients admitted with ADHF, rates of diagnostic coronary angiography are relatively low overall: OPTIMIZE –HF 8.7 % [36]; ADHERE 10 % [25]; EHFS 16 % [27]; and EHFS II 36.5 % (EHFS II reported angiography within a year of hospitalization) [7]. In OPTIMIZE-HF, 18.6 % of patients presenting with de novo heart failure underwent coronary angiography [36]. Rates of coronary revascularization were relatively low: ADHERE 8.1 % PCI, 1.8 % CABG [25]; EHFS PCI 4 %, CABG 3 % [27]; EHFS II PCI 8.4 %, CABG 1.8 % [7]; OPTIMIZE-HF 1.3 % PCI, 1.0 % CABG [37].

In OPTIMIZE-HF, patients with CAD who did not undergo revascularization had a higher post-discharge mortality compared to patients without CAD (10.6 vs 6.9 %). Patients who did undergo revascularization during HF hospitalization had a similar post-discharge mortality compared to patients without CAD [36].

The data from the OPTIMIZE-HF registry was analyzed to determine if the performance of coronary angiography during the index HF hospitalization had an impact on care and post-discharge outcome [37]. 8.7 % of all patients underwent coronary angiography. 27.5 % of patients who underwent angiography also had in-hospital revascularization. Patients with CAD who underwent angiography were more likely to be treated with aspirin, statins, B-blockers, and angiotensin converting enzyme inhibitors at the time of discharge. In patients with CAD, the use of in-hospital coronary angiography was associated with a significantly lower mortality and rate of rehospitalization in the first 60–90 days after adjustment for multiple comorbidities (mortality HR 0.31; p = 0.004; death or rehospitalization HR 0.65; p = 0.003) when compared to patients with CAD who did not undergo coronary angiography. This data suggests that early coronary angiography and revascularization may be beneficial in patients admitted to the hospital with CAD and ADHF.

These results were registry based and may not account for unmeasured variables or selection biases. In the randomize Surgical Treatment for Ischemic Heart Failure (STICH) trial, there was no difference in death from any cause in patients with LVEF ≤ 35 % and coronary artery disease amenable to CABG randomized to medical therapy or medical therapy plus CABG on intention to treat analysis. However, when early crossovers were considered, “on-therapy” CABG was associated with a lower mortality at 5 years (25 % vs 42 %; HR 0.50; p=0.008). Myocardial viability or inducible myocardial ischemia did not identify patients with a differential survival benefit from CABG compared to medical therapy alone [38–40].

Practice guidelines provide recommendations on the use of coronary angiography in the evaluation of patients with chronic heart failure. However, they do not give specific recommendations about the timing of invasive evaluation of coronary anatomy and specifically do not provide recommendations about indications for coronary angiography in patients hospitalized for ADHF. Given the absence of definitive data concerning coronary angiography and revascularization in ADHF, decisions should be individualized based on patient preference, symptoms, clinical presentation, comorbidities, candidacy for revascularization and willingness to undergo revascularization [1, 2]. In general, coronary angiography is recommended for patients with heart failure and symptoms suggestive of angina to assess for the possibility of revascularization. Non-invasive imaging or coronary angiography is recommended for patients with new onset heart failure, no angina and unknown CAD status and patients with new or worsening heart failure without obvious cause, no angina and known CAD. Recommendations from the HFSA Guidelines for the evaluation for CAD in patients with ADHF are reviewed in Table 10.3 [2].

Hypertension is an important precipitant of decompensated heart failure, especially among blacks, women and patients with HFpEF. In the OPTIMIZE-HF registry, poorly controlled hypertension was a precipitating factor in 10.7 % of patients [24]. In the ADHERE Registry, almost 50 % of patients admitted with decompensated heart failure has an initial blood pressure of >140/90 mmHg [25]. Medical non-adherence with antihypertensive medications may result in an abrupt increase in blood pressure and precipitate worsening heart failure or acute pulmonary edema [1, 41].

Arrhythmia was a precipitating factor of heart failure decompensation in 13.5 % of patients enrolled in the OPTIMIZE-HF registry [24]. Atrial fibrillation (AF) is present in approximately 30–40 % of patients hospitalized with ADHF [7, 27, 35, 42–45]. New onset or newly diagnosed AF has been reported to occur in approximately 20 % percent of patients admitted with ADHF [35, 44, 45]. AF is associated with the loss of coordinated atrial contraction. In patients with heart failure and especially in patients with HFpEF, this may be associated with significantly decreased left ventricular filling, increased PCWP and decreased cardiac output. In AF with rapid ventricular response, ventricular filling is further compromised and myocardial ischemia and/or pulmonary edema may be precipitated [46, 47].

Atrial flutter, other supraventricular tachyarrhythmias and ventricular tachycardia may also precipitate acute heart failure. Frequent premature ventricular contractions (PVCs) may be associated with a distinct cardiomyopathy (PVC-related cardiomyopathy) or worsening heart failure and LV dysfunction in the setting of a preexisting cardiomyopathy. In general, a PVC burden of approximately 20–24 % of all QRS complexes on a 24 h Holter monitor identifies a patient with LV systolic dysfunction who may improve with PVC ablation [48–51].

Excessive sodium and fluid intake may contribute to heart failure decompensation. In the OPTIMIZE-HF Registry, non-adherence to diet was identified as a precipitating factor in 5.2 % of patients hospitalized for ADHF. Non-adherence to medication was a precipitating factor in 8.9 % of patients [24]. Non-adherence with diet or HF medication has been reported to be an even more common precipitating factor in some single-center studies [52, 53]. Factors that have been associated with medical non-adherence include more advanced NYHA functional class, minority ethnicity, lower financial status, and lack of perceived social support. Patient perception of barriers to medication adherence may also be fundamental to poor adherence. Frequently reported barriers include: forgetting to take medication, cost, too many pills taken per day, too frequent medication schedule and the belief that skipping one dose of medication will not have an adverse impact on the patient’s condition [54, 55].

Patients with heart failure commonly have excessive and bothersome thirst mediated by activation of central arterial volume receptors and increased levels of angiotensin II both of which stimulate thirst centers in the brain. This leads to excessive sodium and water intake [56–59]. This is a particularly difficult issue in patients with severe heart failure who are not able to be treated with an ACE inhibitor or ARB at reasonable or target dose. In addition, older patients commonly have chemosensory deficits that decrease salt detection and sensitivity and increase salt affinity and intake. Salt affinity may be modifiable toward normal after >2 months of sodium restriction [60]. Patients may also be unaware of the salt content of foods they are consuming or may feel that they do not need to limit sodium intake. A careful review of the patient’s history of dietary intake of sodium and free water (including “hidden” sources of free water such as fruit) is an important part of the assessment of patients admitted with ADHF.

Pneumonia and other acute respiratory processes were the most common precipitating factor (15.3 %) identified in patients hospitalized for ADHF in the OPTIMIZE-HF registry [24]. Pulmonary infections may alter pulmonary function, cause hypoxia, and increase metabolic demands and are poorly tolerated by patients with heart failure. Pulmonary congestion in a patient with chronic obstructive pulmonary disease can compromise already marginal pulmonary function. Patients with heart failure are hypercoagulable and pulmonary embolus may be a cause of HF decompensation [61–64]. Sleep disordered breathing is very common in patients with heart failure. It may worsen heart failure by causing hypoxia, increasing sympathetic nervous system activation and causing or worsening systemic hypertension. Sleep disordered breathing has also been associated with left ventricular remodeling, endothelial dysfunction with progression of coronary artery disease, left ventricular hypertrophy and atrial fibrillation [65–67].

Systemic bacterial or viral infection (pneumonia, urinary tract infection, influenza) are common precipitants of worsening heart failure. Infections increase metabolic demands. In addition, sepsis can cause reversible myocardial dysfunction likely mediated by release of pro-inflammatory cytokines [68, 69].

Hypothyroidism and hyperthyroidism can cause or worsen heart failure. All patients seen for ADHF should have thyroid function studies obtained on admission. Approximately 20 % of patients admitted with ADHF are treated for thyroid disease and should have their therapy reevaluated during hospitalization [70, 71]. Amiodarone-induced hyperthyroidism (AIT) can cause severe worsening of heart failure with or without new or worsening arrhythmias and can be difficult to treat. The clinical presentation of AIT is variable and is often similar to other forms of thyrotoxicosis. However, AIT often occurs in elderly patients and may be “apathetic” with atypical symptoms such as reduced appetite and depression and absence of hyperactivity, tremor, nervousness and heat intolerance [72].

A number of non-cardiac medications can precipitate worsening heart failure. Non-steroidal anti-inflammatory drugs and COX-2 inhibitors inhibit the physiologic production of vasodilatory and natriuretic prostanoids in the kidney and promote sodium and water retention, worsen renal function, inhibit the effect of ACE inhibitors, contribute to diuretic resistance and are associated with a significantly increased risk of hospitalization for heart failure [73].

The thiazolidinediones (TZD), (pioglitazone and rosiglitazone) used to treat diabetes, have been associated with the development of lower extremity edema and new or worsening heart failure [74]. These side effects are primarily due to fluid retention caused by TZD stimulation of the peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ-mediated activation of the collecting duct epithelium’s sodium channel (ENaC) and stimulation of sodium transporters in the proximal tubule contribute to salt and water retention [75, 76]. In addition, TZDs reduce systemic vascular resistance and may cause fluid extravasation by exposing the capillaries of the lower extremities to higher perfusion pressures. TZDs also increase the concentration of vascular endothelial growth factor which is a potent inducer of vascular permeability which may predispose patients to edema [77].

Insulin can also cause sodium retention mediated by stimulation of a broad range of sodium transporters in the proximal tubule, loop of Henle and distal tubule [74]. Pregabalin, which is frequently used to treat diabetic peripheral neuropathic pain, has also been reported to precipitate heart failure decompensation [78].

Cardiotoxicity is a common complication of many conventional and targeted biological anti-cancer medications [79–83]. Cocaine, excessive alcohol intake, and methamphetamine are associated with worsening heart failure [84–89].

A number of cardiac medications have negative inotropic properties and can worsen heart failure. Recent initiation or uptitration of β-blockers has been associated with worsening heart failure, especially in patients with severe ventricular dysfunction and those recently treated with inotropic agents. Calcium channel blockers (CCBs), especially the non-dihydropyridine CCBs, have been associated with worsening heart failure. A large number of antiarrhythmic agents may also precipitate worsening heart failure including quinidine, procainamide, disopyramide, flecainide, sotalol, propanone, and dronedarone.

Right ventricular pacing can lead to abnormal electrical and mechanical activation patterns (referred to as ventricular “dyssynchrony”) which lead to adverse effects on left ventricular performance and hemodynamics, subsequent adverse effects on cardiac structure and function, and clinical heart failure.

Patients with a single lead pacemaker or ICD may develop gradually progressive sinus bradycardia in response to beta blocker or amiodarone therapy and present with worsening heart failure in the setting of recent onset ventricular pacing. A similar scenario may be seen in patients who develop atrial fibrillation with a slow ventricular response in the setting of beta blockade or amiodarone therapy. These patients may improve by pacemaker reprogramming that minimizes RV pacing or an upgrade to a device that provides biventricular pacing [90, 91].

Renal dysfunction is common in patients with ADHF. In the ADHERE registry, chronic renal insufficiency was reported in 30 % of patients and 21 % had a creatinine >2.0 mg/dL [25]. In OPTIMIZE-HF, the mean creatinine was 1.8 mg/dL [92]. Elevated BUN and creatinine may be manifestations of renal hypoperfusion in the setting of low cardiac output, high filling pressures and/or neurohormonal activation. In HF, renal cortical blood flow is especially decreased and tubulointerstitial damage may develop due to decreased local renal perfusion and increased venous congestion. Albuminuria can occur in heart failure and is a manifestation of both a loss of glomerular integrity and tubular damage. A high albumin load may also contribute to tubular damage [93]. In addition, patients with heart failure commonly have risk factors for both cardiac and renal disease including diabetes and hypertension that may contribute to renal insufficiency independent of hemodynamic derangements from heart failure. A gradual or acute reduction in renal function will decrease renal clearance of sodium and water, worsen diuretic resistance, contribute to inadequate blood pressure control, contribute to hyperkalemia, and worsen anemia all of which will contribute to worsening HF.

Benign prostatic hypertrophy is common in men over the age of 50 years and may contribute to urinary obstruction, impaired renal function and worsening heart failure in men with ADHF. The prevalence of histologically diagnosed prostatic hyperplasia increases from 40 to 50 percent in men age 51 to 60 years, to over 80 percent in men older than age 80 years [94]. A population based study from Olmstead County, Minnesota found that moderate to severe lower urinary tract obstructive symptoms were present in 13 % of men 40–49 years and 28 % of those older than 70 years [95]. An evaluation for urinary obstruction can easily performed using bladder scanning. We have found that routine bladder scanning of men hospitalized with ADHF who have an elevated creatinine or diuretic resistance is helpful in identifying lower urinary tract obstruction. Relief of urinary obstruction with placement of a urinary catheter commonly results in improvements in renal function, diuretic resistance, pulmonary and systemic venous congestion and heart failure symptoms.

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