Management of Hypertension in Chronic Heart Failure

Saraswathy Manickavasagam; Ramanna Merla; Michael M Koerner; Ken Fujise; Sanjay Kunapuli; Salvatore Rosanio; Alejandro Barbagelata

Disclosures

Expert Rev Cardiovasc Ther. 2009;7(4):423-433. 

In This Article

HTN in Patients with HFNEF

The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) Registry confirmed the high prevalence of HFNEF and indicated that their postdischarge mortality and hospitalization rates are similar to those with HFREF.[68] Nevertheless, we lack reliable data on the optimal management of these patients. HTN frequently coexists, and a recent study cites HTN as the cause of approximately 61% of HFNEF cases. Many patients will have LV hypertrophy and approximately two-thirds will have diastolic dysfunction as well.[32]

For these patients, the AHA/ACC recommend a lower target blood pressure than for uncomplicated HTN (i.e., less than 130/80 mmHg[17,19,69]), since higher blood pressures continue to worsen ventricular structure and performance. Increases in systolic blood pressure slow myocardial relaxation,[70] and hypertrophy increases passive chamber stiffness. Fortunately, blood pressure control will eventually improve diastolic function in these patients.[17] However the blood pressure that may be achieved without adversely affecting cardiac output will vary widely from patient to patient.

Renin-angiotensin Inhibitors

Angiotensin receptor blockade has been well studied in patients. The CHARM-Preserved trial showed that candesartan reduced hospitalizations of patients with class II-IV CHF whose ejection fraction was greater than 40%, although it did not significantly reduce cardiovascular death. In another study, losartan improved exercise tolerance and quality of life.[17] LV hypertrophy may regress to a greater degree with angiotensin receptor blockade than ACE inhibition. A meta-analysis examining the efficacy of antihypertensive drugs in reversing LV hypertrophy in patients with HTN illustrated that angiotensin receptor blockade and ACE inhibition decreased LV mass index by 13 and 10%, respectively.[71] Such regression may improve diastolic function; however, another large randomized trial showed that valsartan had no such effect.[72,73] The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial showed no significant decrease in cardiovascular mortality or morbidity measured by death, hospitalization and quality of life in patients with HFNEF who were randomly treated with an ARB-irbesartan or placebo. There was a significant increase in serum creatinine and hyperkalemia in the ARB arm though these did not translate to significant clinically adverse events.[18]

The AHA/ACC guidelines recommend ACE inhibition, but no studies have clearly demonstrated these medicines benefit patients with HFNEF. In the OPTIMIZE-HF Registry, ACE inhibition did not improve the mortality or readmission rates of these patients.[74] However, it should be considered for HFNEF patients who have symptomatic coronary disease, or diabetes and another risk factor. It can reduce symptoms, ventricular mass, and myocardial stiffness.[24,75] These drugs should be titrated carefully to avoid hypotension, since the poor diastolic function of these patients may make them very preload dependent.

Aldosterone Antagonist

Aldosterone promotes hypertrophy and fibrosis and may be partly responsible for the diastolic dysfunction that occurs with age and HTN.[76] Small studies have suggested benefits of aldosterone blockade[77] and prompted the larger Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) NIH trial, which is now enrolling subjects.

β-adrenergic Receptor Blockade

Patients with HFNEF respond well to β-adrenergic receptor blockade, and the Heart Failure Society recommends these medications for treating HTN with HF.[24] In addition to lowering blood pressure, these agents increase diastolic filling time and, thus, enhance ventricular filling and coronary perfusion. They also decrease the ventricular rate response to atrial arrhythmias and induce regression of hypertrophy.[24,78] Carvedilol may reduce the symptoms and repeat hospitalizations of these patients.[79] In a large study of over 4000 patients, initiation of β-blockers at discharge in patients with HFNEF was not associated with a significant decrease in 1-year mortality or rehospitalization.[25]

Many of these patients with HF have other conditions that β-blockade is very likely to benefit, such as a prior myocardial infarction and atrial fibrillation and, hence, should be included for HTN management in these scenarios.

Calcium Channel Blockade

Unlike HF patients with reduced systolic function, HFNEF patients are likely to benefit from calcium channel blockade. Amlodipine may be especially helpful in HFNEF patients with HTN and limiting angina, in whom the drug may decrease both blood pressure and the number of ischemic episodes.[19] Again, as with any agent that suddenly reduces preload in patients with diastolic dysfunction, dose titration must proceed carefully. The Heart Failure Society highly recommends nondihydropyridine agents (e.g., verapamil and diltiazem) for HFNEF patients with atrial fibrillation that cannot tolerate β-receptor blockade or whose heart rates do not decrease sufficiently in response to it.[19] Verapamil may be particularly helpful because it can improve myocardial relaxation and compliance

Diuretics

No major study has shown that diuretics benefit HFNEF patients and, in HFNEF patients with HTN, diuretics are recommended only if the patients are also volume overloaded. In these cases, one may begin with either a thiazide or loop diuretic, or advance from a thiazide to a loop diuretic if the former proves inadequate.[19] As before, one must avoid excess preload reduction.

Nitrates & Hydralazine

Excess preload reduction and sudden blood pressure declines are especially likely when treating HFNEF patients with these agents, and they should be used with caution.

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