It is recommended that evidence-based therapy for HF be used in the elderly patient, with individualized

consideration of the elderly patient’s altered ability to metabolize or tolerate standard medications. (Level of Evidence: C)

Class IIa

The addition of isosorbide dinitrate and hydralazine to a standard medical regimen for HF, including ACEIs and beta-blockers, is reasonable and can be effective in blacks with NYHA functional class III or IV HF. Others may benefit similarly, but this has not yet been tested. (Level of Evidence: A)

Many patients with HF are members of subpopulations who are likely to exhibit unique responses that accelerate the development or progression of HF or complicate the man- agement of HF.

5.1. Women and Men

Many physicians regard HF primarily as a disease of men, because coronary risk factors are common in men and pri- marily men are enrolled in clinical trials of treatments for HF; however, the majority of patients with HF in the gener- al population are women (particularly elderly women), who frequently have HF associated with a normal LVEF (27). Even HF due to reduced LVEF may be different in women than in men. Yet, most large, multicenter trials have not included sufficient numbers of women to allow conclusions about the efficacy and safety of their treatment. Several stud- ies have documented a lower use of ACEIs in women with HF than in men (511), and another study reported that gical reconstruction techniques offer “rescue therapy” to

patients with critical hemodynamic compromise.

The use of mechanical circulatory assist devices in end- stage HF is an area of intense investigation. Extracorporeal devices can be used for short-term circulatory support in patients who are expected to recover from a major cardiac insult (e.g., myocardial ischemia, postcardiotomy shock, or fulminant myocarditis). Left ventricular assist devices pro- vide similar degrees of hemodynamic support; many are implantable and thus allow for long-term support, patient ambulation, and hospital discharge (507). Most clinical experience with these devices has been derived from their use in patients being “bridged” to transplant. The completion of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial investigated the use of these devices as permanent or “desti- nation” therapy in selected non–transplant-eligible patients. This trial enrolled 129 patients, for whom 2-year survival was 23% in the 68 patients treated with the device and 8% in the 61 patients who received medical therapy (508). Device- related adverse events were numerous and included bleeding, infection, thromboembolic events, and device failure. This trial established the efficacy of device therapy for end-stage HF. Improvements in newer generations of devices will hopefully permit even further prolongation of survival. Presently, destination device therapy is anticipated to benefit those patients predicted to have a 1-year survival of less than 50%. One such group could be the population of non–trans- plant-eligible patients requiring continuous intravenous inotropic infusions. Some reports have suggested that pro- longed mechanical decompression of the failing heart may

Table 10.Indications for Cardiac Transplantation

Absolute indications in appropriate patients

For hemodynamic compromise due to HF

•Refractory cardiogenic shock

•Documented dependence on IV inotropic support to maintain adequate organ perfusion

•Peak VO2less than 10 mL per kg per min with achievement of

anaerobic metabolism

Severe symptoms of ischemia that consistently limit routine activity and are not amenable to coronary artery bypass surgery or percutaneous coronary intervention

Recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalities

Relative indications

Peak VO211 to 14 mL per kg per min (or 55% of predicted) and

major limitation of the patient’s daily activities

Recurrent unstable ischemia not amenable to other intervention Recurrent instability of fluid balance/renal function not due to

patient noncompliance with medical regimen

Insufficient indications

Low left ventricular ejection fraction

History of functional class III or IV symptoms of HF

Peak VO2greater than 15 mL per kg per min (and greater than 55%

of predicted) without other indications

HF indicates heart failure; IV, intravenous; and VO2, oxygen consumption per unit time.

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the diagnosis is made, HF progresses more rapidly in black than in white patients, as evidenced by a higher risk of initial and recurrent hospitalizations (520-522). This risk cannot be explained by the presence of epicardial coronary artery dis- ease or documented MI, both of which are less common in black than in nonblack patients with HF. The data are not clear as to whether a definitive increase in mortality risk exists (520-522).

The literature is mixed on whether blacks with HF more frequently receive suboptimal inpatient care for their HF (523, 524). However, deficiencies in cardiovascular risk fac- tor evaluation and disease detection and treatment as well as in access to quality outpatient care may contribute to the increased incidence and morbidity of blacks with HF (525- 527).

Blacks and other racial minorities with HF are underrepre- sented in most clinical trials of HF, which compromises the extrapolation of results from major clinical trials to ethnic subgroup populations. To date, there are no data to suggest that any significant treatment variance from standard care for HF should be acceptable in any particular group. Clinical experience suggests that Asian patients have a higher than average risk of cough during treatment with an ACEI. Retrospective analysis of subgroup data has suggested that, as in the treatment of hypertension, black patients with HF may experience less efficacy than nonblacks from the use of ACEIs (528). A recent analysis of a large ACEI HF trial that used a matched-cohort design confirmed that black patients had a greater number of hospitalizations for HF than matched white patients (529). However, rates of death in that trial were similar between black and nonblack patients with HF (529). Interestingly, the results of 2 trials evaluating the effects of different beta-blockers in black patients have been discordant: bucindolol caused a nonsignificant increase in the risk of a serious clinical event in black patients, but it reduced deaths and hospitalizations in nonblack patients (530). Thus, bucindolol may represent a decidedly different beta-blocker than those already approved for the treatment of HF. Conversely, the benefit of carvedilol in a separate series of trials was apparent and of a similar magnitude in both black and nonblack patients with HF (531). There may be race-based differences in the outcome of cardiac transplanta- tion as well (532). Further study is needed to clarify these issues.

The emerging field of genomic medicine has begun to sug- gest that important variances in the expression of certain high-risk, single-nucleotide polymorphisms may be evident along racial lines and may provide a physiological basis for differences in the natural history of HF and differences in drug responsiveness (533-536). Data from these early inves- tigations are not yet definitive; racial groupings are neces- sarily heterogenous, and data will need to be interpreted cau- tiously.

A prospective, double-blind randomized trial conducted specifically in blacks with NYHA class III/IV HF has been completed (356) . The patient population was characterized by a much higher likelihood of a nonischemic cause of HF women are given fewer cardiovascular medications after an

MI than men (510, 512, 513). These findings may explain why women have been noted to rate their quality of inpatient care lower than men and why they have less improvement in physical health status after an episode of HF (510). Some analyses have suggested that women with HF, particularly with asymptomatic reduced LVEF, may not show survival benefits from ACE inhibition (514, 515). Women may also have a different safety profile than men, as evidenced by their higher risk of ACEI-induced cough (516). The conflict- ing data regarding the efficacy of digoxin in women suggests that if it is prescribed, particular attention should be paid to dosing and renal function (314). Currently, great efforts are being made (and mandated) to include a higher proportion of women in government-sponsored trials.

Because HF is frequently accompanied by erectile dys- function, men may express interest in the use of a phospho- diesterase type 5 inhibitor (e.g., sildenafil) as a means of enhancing sexual performance. Few patients with HF were enrolled in controlled trials with sildenafil, and thus, the effi- cacy and safety of this drug in patients with HF are not known. Nevertheless, recent studies suggest that sildenafil may produce hemodynamic benefits in patients with coro- nary artery disease and may act to improve some of the peripheral vascular abnormalities that characterize patients with HF (517). Although patients with HF appear to tolerate short-term administration of the drug without difficulty, sildenafil should not be given to patients taking nitrates, who may experience profound hypotension due to its ability to potentiate the systemic vasodilator effects of drugs that increase intracellular levels of cyclic guanosine monophos- phate (518).

5.2. Ethnic Considerations

Race is an imprecise concept that has largely become a social and political construct, with more limited biological signifi- cance (519). The concept of racial “minorities” may be rele- vant to large populations, especially those in clinical trials, but is clearly not a concept applicable in many demographic areas and clinical practices. However, it is useful to review epidemiological and clinical trial evidence to raise awareness of potential areas of concern and guide socioeconomic and clinical remedies. This has become especially pertinent in the evaluation of HF as it affects blacks, although much more information is also needed about the effects of current and new therapies in the Hispanic population. Heart failure is a major public health problem in blacks. Heart failure is more common in the black population, affecting approximately 3% of all black adults. This reflects a 50% higher incidence of HF in the black population than is seen in the general pop- ulation.

Black patients develop symptoms of HF at an earlier aver- age age than nonblacks, possibly because black patients are more likely to have hypertension and diabetes mellitus than nonblacks and because they more frequently exhibit sodium retention, ventricular hypertrophy, and vascular injury. Once

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2. Physicians should control systolic and diastolic hyper-