Ambulatory Care Management in Low Blood Pressure Patient with HFrEF

Abstract

Heart failure (HF) affects an estimated 38 million people globally, with most published research estimating a prevalence of 1 to 2% of the adult population. Low blood pressure (BP) is reported in 10 to 15% of patients with HF in clinical trials, although this proportion is much more frequent in routine clinical practice. Low BP in outpatients has a better outcome compared to inpatients. Low BP is often a restricting factor in the use and uptitration of guideline-directed medical therapy (GDMT). A 57-year-old male presented himself to the HF clinic with complaints of bloating, shortness of breath, and fatigue. The patient had a history of acute coronary syndrome and cardiac arrest, but the results of coronary angiography showed nonsignificant coronary artery disease. Cardiomegaly was seen on chest X-ray. Electrocardiogram showed pathologic q wave II, III, and AvF with poor r wave progression on V1-V6. The patient was admitted due to acute decompensated HF with hypotension. After the initial decongestion patient was treated with sacubitril/valsartan, bisoprolol, and spironolactone in the outpatient clinic. Patient complaints and BP slowly improved during the outpatient phase. Hypotension remains a challenge in implementing GDMT in HF patients. By following the steps according to algorithm and current guidelines, GDMT can be optimized in these patients.

Heart failure (HF) is one of the malignant cardiac syndromes which has a high morbidity and mortality rate all over the world. ¹ In addition, HF is also the main cause of poor quality of life and places a substantial financial burden on health care systems worldwide. HF affects an estimated 38 million people globally, with most published research estimating a prevalence of 1 to 2% of the adult population. According to data from Europe and North America, HF accounts for 1 to 2% of all hospital admissions, or more than 1 million admissions each year, with 80 to 90% of these admissions attributable to chronic HF decompensation. ² International guidelines make clear recommendations as to which evidence-based drugs should be prescribed for patients with HF with reduced ejection fraction (HFrEF). ³ The World Health Organization has projected that the largest increases in cardiovascular disease worldwide are occurring in Asia. ⁴ Meanwhile, at the National Cardiovascular Center in Jakarta, HF is the most common diagnosis with high mortality. ⁵

Low blood pressure (BP) is a very common condition that occurs in patients with low ejection fraction HF. And symptomatic hypotension, although rare, is a condition that greatly affects the treatment of HF. This condition can be described as a sign of advanced stage pump failure, and besides that, it can also be a side effect of HF therapy, and thus it becomes a challenge in optimizing medication according to the HF guidelines (guideline-directed medical therapy [GDMT]). ⁶ Low BP is reported in 10 to 15% of patients with HF in clinical trials, although this proportion is much more frequent in routine clinical practice. ⁷ Achieving the target therapeutic dose becomes a challenge because of the possibility of a decrease in BP when the drug dose is increased. The exact incidence of low BP in the HFrEF population in Indonesia especially in National Cardiovascular Center Harapan Kita (NCCHK) is not yet available, but from the ongoing registry (ANCHUR registry), the prevalence of low BP in the HFrEF population in NCCHK is about 11.7%. Low BP (< 90 mm Hg) has been repeatedly emphasized as a marker of poor outcomes in acute HF. In contrast, the prognostic value of low BP in ambulatory chronic HF appears attenuated. Systolic BP (SBP) association with outcome in ambulatory patients does not necessarily imply that lower SBP is causally related to poorer outcomes. The attenuated association between BP and outcome in ambulatory patients compared to acute settings and the uncertainties regarding causality advocate for maintaining HFrEF life-saving drugs despite low BP. Low BP is a factor often found to limit the use and uptitration of class I life-saving drugs in HFrEF and can prompt stopping (at best temporarily) these drugs. However, all HF patients should receive optimal care as per the Guideline Directed Medical Therapy (GDMT), because this therapy has been shown to reduce hospitalization rates, morbidity, and mortality. ⁸

Case Illustration

A 57-year-old male presented himself to the HF clinic of NCCHK with the chief complaint of fatigue and bloated feeling. The patient had a history of coronary artery disease previously treated with fibrinolytic agents in a general hospital. During fibrinolytic administration, the patient fell into cardiac arrest but was successfully resuscitated.

The patient was then referred to the NCCHK where coronary angiography was performed revealing a normal coronary with slow flow Thrombolysis in Myocardial Infarction 2 flow in the left anterior descending artery and no stenosis. The patient was then discharged on medications; however, this patient went “Doctor shopping” in our center, and during this period, this patient due to complaints of feeling bloated in the stomach was also seen by an internist and an endoscopy was performed which revealed normal results.

The patient also complained of shortness of breath while lying flat, nausea, and swollen legs. Previous medications were candesartan 1 × 4 mg and bisoprolol 1 × 2.5 mg. With residual symptoms of shortness of breath and swelling of the legs, the patient then presented himself to the HF clinic where we performed a series of examination.

In the initial physical examination in the HF clinic, the patient was fully conscious and looked moderately ill with a BP of 79/56 mm Hg, heart rate of 65 beats per minute (bpm), respiratory rate 18 times per minute, temperature was 36.°C, and peripheral oxygen saturation was 99%. Elevation of jugular venous pressure was observed. Auscultation of the heart revealed normal S1 and S2, regular rate, and pansystolic murmur grade 3/6 was heard in the lower left sternal border without gallop. Lung auscultation revealed vesicular pulmonary sounds with no rales or wheezing. Abdominal examination revealed positive hepatojugular reflux. Slight bilateral pitting edema was seen on both lower extremities. Laboratory results revealed normal renal function and mild hyponatremia with leukocytosis. N-terminal pro-brain natriuretic peptide laboratory assays were not done at this point. Chest X-ray revealed cardiomegaly (cardiothoracic ratio 59%), normal right heart border, normal aortic segment, and normal pulmonary artery, downward cardiac apex was seen, and no infiltrate was seen ( Fig. 1A ).

Fig. 1.

( A ) Chest X-ray. ( B ) Electrocardiogram (ECG) of the patient during the initial presentation.

Electrocardiogram showed sinus bradycardia with a rate of 48 bpm, left axis deviation, and pathologic Q wave on lead II, III, and aVF. Wide biphasic P wave on V1-V2. Poor R wave progression on V1-V6. Echocardiography showed biventricular failure with an ejection fraction of 16%, tricuspid annular plane systolic excursion 1.3 cm, left ventricular (LV) apical thrombus, and severe tricuspid regurgitation ( Fig. 1B ).

Based on history taking, physical examination, and supporting examination, the patient was diagnosed with congestive HF with functional class III due to acute decompensated HF in congestive HF due to old anterior myocardial infarction, mild cognitive impairment, and hypotension.

The patient was initially treated with oral sacubitril/valsartan 2 × 25 mg, spironolactone 1 × 25 mg, bisoprolol 1 × 1.25 mg, and intravenous furosemide injection for optimization of decongestion. The patient was also monitored for clinical deterioration, signs of hypoperfusion, worsening renal function, and electrolyte imbalance. During the initial decongestive outpatient period, the patient was advised to go to the HF clinic weekly for a weekly furosemide injection ( Figs. 2 3 4 ). After 4 weeks of outpatient therapy, sacubitril/valsartan was increased to 2 × 50 mg and the patient reported improvement in bloating. On physical examination, there were no signs of hypoperfusion. At the next follow-up, spironolactone was discontinued due to the development of gynecomastia. In the following month, the dose of sacubitril/valsartan was increased to 2 × 100 mg and furosemide 1 × 40 mg was added daily. With these changes, the patient no longer complained of bloating and reported an increase in appetite and improvement in physical activity. Three months after initial hospitalization, sacubitril/valsartan was increased to the maximal dose of 2 × 200 mg, while furosemide 1 × 40 mg, and bisoprolol 1 × 1.25 mg was continued. During the recent encounter the patient has significantly improved, the patient reported an increase in physical activity, and minimal symptoms, and additional medication using empagliflozin was planned.

Fig. 2.

( A ) Patient's echocardiography after discharge. ( B ) Ejection fraction measurement on outpatient clinic after initial discharge.

Fig. 3.

( A ) Course of kidney function (glomerular filtration rate [GFR]) during therapy. ( B ) Course of electrolytes during therapy.

Fig. 4.

Patient's course of ejection fraction and tricuspid annular plane systolic excursion (TAPSE).

During a visit to the HF clinic, education is always given on how to take medication correctly, self-weighing, and recognize signs of hypoperfusion at home. At the clinic, the signs and symptoms of hypoperfusion are monitored regularly, and electrolytes and kidney function are checked regularly.

Discussion

HF is not a single pathological diagnosis, but a clinical syndrome consisting of cardinal symptoms (e.g., breathlessness, ankle swelling, and fatigue) that may be accompanied by signs (e.g., elevated jugular venous pressure, pulmonary crackles, and peripheral edema). It is due to a structural and/or functional abnormality of the heart that results in elevated intracardiac pressures and/or inadequate cardiac output (CO) at rest and/or during exercise. Diagnosis of HFrEF requires the presence of symptoms and/or signs of HF and a reduced ejection fraction (LV ejection fraction [LVEF] <_40%). ⁹ While low BP was defined as SBP < 90 mm Hg in the 2016 European Society of Cardiology (ESC) guideline for HF. ¹⁰

BP has two main components: a pulsatile component related to arterial stiffness mostly associated with pulse pressure or SBP, and a steady component related to systemic vascular resistance mostly associated with mean BP and diastolic BP. In patients with impaired LVEF, both SBP and pulse pressure are primarily dependent on LV stroke volume, while the mean BP is highly dependent on total blood volume and the degree of peripheral vasodilatation. Low BP in HFrEF may have multiple origins such as low cardiac function, hypovolemia (usually due to diuretics), treatment-related vasodilatation, and altered vasoreactivity related to comorbidities such as diabetes. As for the patient, depressed cardiac function is the most likely contributor to low blood pressure.

The neurohormonal mechanisms that are activated in HF are identical to those that are triggered when mean arterial pressure and CO are threatened in situations like intense physical exercise or hemorrhage. In these circumstances, the neurohormonal mechanisms are successful at reversing these temporary hemodynamic abnormalities, and their activity eventually subsides. In contrast, however, this neurohormonal activation is incessant in HF. These systems are constantly on in an attempt to compensate for the failing heart's inability to maintain normal cardiovascular homeostasis. The chronic presence of these circulating neurohormones exacerbates the hemodynamic abnormalities present in HF which encourage further remodeling and neurohormone release and further hemodynamic deterioration. Continued progression of HF eventually leads to a critical reduction in blood flow to all vital organs. In this final phase, the body maximizes all of its vasoconstrictive mechanisms in an attempt to redirect blood flow to these critical organ systems, which only add to the hemodynamic burden of the failing heart; thus, ventricular function progressively deteriorates, and terminal HF ensues. A vicious cycle develops whose result is progressive ventricular dysfunction and death. ⁵

HFrEF is characterized by the presence of signs and symptoms of HF with an LVEF < 40%. Siswanto et al, ⁵ conducted an Acute Decompensated Heart Failure Registry in 2006 with the involvement of five hospitals, including the National Cardiovascular Center (NCVC) Jakarta, which is the main cardiovascular referral hospital in Indonesia, and as a result, coronary artery disease has a prevalence of 49.9%. ¹¹ Another finding is, HF in men is twice as common as in women, at a younger age than in other countries (mean 55 years old at NCVC and 60 years old at other Indonesian hospitals). Meanwhile, according to the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic HF, hypotension is defined as SBP < 90 mmHG. ¹⁰ As for the patient presented in this case presentation, 57 years old male with a sign and symptom of HF with a baseline LVEF of 16% and baseline SBP of 73 mmHg, with a history of coronary artery disease. Cautela et al provided an algorithm to approach low BP in ambulatory HFrEF. This algorithm offers practical steps to manage a patient with HFrEF with low BP in an outpatient setting. The general rule of this algorithm is to maintain a low dose of all HFrEF classes of drugs rather than using a high dose of a single drug. As for the patient, he had a low ejection fraction and low BP. ⁷

It is very clear that in a hemodynamically unstable condition, the patient requires treatment. The link between symptoms suggestive of hypotension (dizziness, fatigue, especially when standing up and in an upright position) and low BP must be established. In the absence of orthostatic hypotension, ambulatory BP monitoring (ABPM) may be considered to detect hypotensive episodes related to symptoms. When SBP is below < 90 mm Hg with clear symptoms of postural or orthostatic hypotension, we recommend going to step II. As for the patient, he had no link between low BP and symptom, and from two times of visits, the BP was still below 90 mm Hg. We did not perform ABPM on this patient. The last medication for the patient is candesartan 1 × 4 mg and bisoprolol 1 × 2.5 mg. Yancy et al stated that angiotensin receptor neprilysin inhibitor (ARNI) is recommended for chronic symptomatic HFrEF NYHA class II or III who tolerates an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. ¹² In this patient, we initiate ARNI with 2 × 25 mg and decrease the bisoprolol dose to 1 × 1.25 mg. SBP was still below < 90 mm Hg, with no sign of hypoperfusion. At the next visit, the shortness of breath is reduced. SBP was still below < 90 mm Hg, with no sign of hypoperfusion. On echocardiography evaluation, the EF improved from 16 to 29% and kidney function was still within normal limits on lab results. With this finding, we decided to uptitrate sacubitril/valsartan to 2 × 50 mg. For the next few visits, diuretics were optimized by administering intravenous loop diuretics. Spironolactone was discontinued due to the side effect of gynecomastia. On the next visit, there were no complaints of shortness of breath and no bloating. However, SBP was still below 90 mm Hg with no sign of hypoperfusion. The dose of sacubitril/valsartan was increased to 2 × 100 mg and at the last visit, the maximum dose was initiated 2 × 200 mg. With these changes, the patient appeared to be in a better clinical state with no hospitalization episode and an improvement of both functional class and quality of life, with kidney function and electrolytes in normal value. We also plan to administer an SGLT2 inhibitor to the patient. ⁹

The causes of hypotension should be investigated. Non-drug-related causes of hypotensive episodes are diarrhea, fever, and dehydration. For correctable causes, therapy for chronic HF does not need to be replaced in the long term. If therapy must be discontinued, early reintroduction should be attempted whenever possible. Cardiovascular treatments are not indicated in HFrEF, such as calcium channel blockers, centrally acting antihypertensive drugs, or alpha-blockers, should be reduced or discontinued, regardless of the form of administration. It is also critical to identify “hidden” hypotensive drugs, such as alpha-blockers in the context of prostate disease or intraocular beta-blockers in the case of glaucoma, and replace the latter with another drug class. As for the patient, he had no hypotensive factors unrelated to HFrEF.

In the absence of congestive signs, diuretics should be carefully decreased. In this patient we carefully tapered down the dose of furosemide into 1 × 40 mg as the patient was also receiving ARNI. Downtitration of diuretic in the presence of ARNI must be done carefully to help avoid hypotensive episodes. ¹³

As per the approach advised by the ESC, the following steps must be taken in assessing hypotension in patients with HF: (1) confirm low BP and assess its link with symptoms, (2) identify hypotensive factors unrelated to HFrEF and stop/reduce non-HFrEF BP-lowering therapies, (3) adjust diuretic doses, and (4) adjust HFrEF treatments according to clinical profile. With these challenges, we also concluded that ABPM will greatly help in adjusting GDMT in hypotensive HF patients. ^{7 13}

Conclusion

Hypotension remains a challenge in implementing GDMT in HF patients. By following the steps according to algorithm and current guidelines, GDMT can be optimized in these patients. All HF patients should receive optimal GDMT therapy. Low BP should not be a barrier in initiating or uptitrating GDMT, because low BP is not the same as hypoperfusion.

Funding Statement

Funding None.