Syncope Beginning in People Over 50 Years Old—Experience in 52 Cases

It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predominant causal factor, which is attributed in many cases to advanced age, metabolic, cardiovascular or neurological diseases, to failure of baroreflexes, all of the above may be associated with the use of hypotensive drugs alone or in combination with psychotropic drugs. Furthermore, causes such as carotid sinus syncope, postprandial syncope and situational syncope become more frequent. Therefore, as people age, they present a favorable pathological terrain for the production of syncope. The older you are, the more likely you are to start with syncope. Finding the definitive diagnosis for their syncopes can be difficult, given the multiplicity of interacting factors. Their study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, concomitant diseases and careful surveillance to get closer to the diagnosis.


Introduction
Syncope and/or lipothymia are common at all ages. However, going over 50 and just starting to present them is unusual. The first peak is during adolescence at age 15 [1]. Its frequency is usually twice as high in women as in men [2] [3].

Pre-Tilt test study and inclusion criteria
This study included retrospective data analysis of 212 patients studied with HUT (60% female), conducted between 2012 and 2018. The mean age of these patients was 31.8 years (range: 6 -89 years).
Only 52 subjects (25%) who consulted for syncope or presyncope, beginning at 50 years or older were included. None had a history of prior syncope.
To rule out a cardiac or other causes, subjects were screened with a medical history, physical examination, an evaluation by a cardiologist and examinations: electrocardiogram (12 lead), echocardiogram, heart rate holter, and sometimes an electrophysiological study. If this review is negative or doubtful, the patient is sent for our neurological evaluation and HUT.
If a cardiac cause was proven the patient was not included. The same if the patient was epileptic or suffered from pseudosyncopes. 80 volunteers of the same age and sex served as controls.
Subjects were recruited from patients of the Militar Hospital from Santiago.

Tilt Test Exam Conditions
Fasting patient, between 8 and 12 hours. Quiet room, with dim light at a temperature between 20˚C -22˚C. Supervised by a neurologist, a cardiologist and a medical technologist. Cardiology personnel installs continuous EKG monitoring.
A hemoglucotest is performed prior to the exam.
Electrocardiographic monitoring and continuous measurement of blood pressure, heart rate and surveillance of doctors and nurses are performed.
Drugs, venous lines, a defibrillator, and equipment for cardiopulmonary resuscitation are available.

Tilt Test Protocol
A record of heart rate (HR) and blood pressure (BP) and of symptoms reported by the patient is kept every 5 minutes. The reason for stopping the examination or any important incident is noted and recorded at any time. The sublingual ni-International Journal of Clinical Medicine troglycerin protocol is based on Del Rosso [10].
Carotid massage is performed on all patients over 60 years of age. Previous discard of murmur or carotid stenosis or stroke in the last 6 months. Five minutes on each side [11].
Tilt Test ends if a "positive HUT" is obtained: This is syncope (loss of consciousness) or presyncope (dizziness, nausea, paleness, etc., announcing that syncope is imminent). Associated with low blood pressure (systolic BP < 70 mmHg) or low blood pressure plus bradycardia, or if intolerable patient discomfort occurs.
If there are no symptoms, it is terminated due to the end of the protocol.
In addition, sympathetic and parasympathetic function tests (Valsalva maneuver and deep breathing test) are performed in order to support or rule out failure in the baroreflexes. For the statistical comparison, Anova and logistic regression are used, and depending on the sample size, a non-parametric test is used.

Ethical Clearance
Our study was analyzed and approved by the institutional ethics committee of the Hospital Militar, and was carried out in accordance with the ethical standards of the Helsinki Declaration 1964. Patients and controls signed an informed consent before inclusion.

Findings in the Tilt Test
The overall positivity of the HUT was 78%, (n: 41), which is common in patients selected by trained doctors and sent to HUT [14] [15] [16].
The most important final events found in the positive HUT were: symptomatic orthostatic hypotension (OH) (n: 24 cases/46%), with final collapse of the patient. Followed by mixed vagal syncope mainly vasodilator n: 11 (21%) and cardioinhibitory vagal syncope with 8% (n: 4). This is shown in Table 4. International Journal of Clinical Medicine Negative Tilt Test: Eleven patients (21%), who consulted for syncope, lipothymia, or orthostatic dizziness had a negative HUT. They were followed up, trying to find a possible cause of their symptoms.
The possible explanation of symptoms in patients with negative HUT can be seen in Table 5.
To consider it as the cause of the condition, hypotension must produce orthostatic symptoms during the HUT [19]. Table 6 shows the number of patients and the probable cause of OH, postulated after an average follow-up of 4.5 years. The n is greater than 24, because   several factors were combined in most of the patients, without being able to assure which is the influence that each one of them weighs. 48 possible combinations were found, which would explain 89% of the causes of OH.

Drug Use and Orthostatic Hypotension
Antipsychotics or antidepressants used were: amitriptyline, trazodone, haloperidol and quetiapine. All were combined with antihypertensive drugs (n: 4).
Five patients were using sertraline, but their syncopes had already started before starting the drug.
Eight of these patients (42%) benefited from the withdrawal or decrease of antihypertensive drugs.

Cardiovascular Comorbidities
In 31 patients we found comorbidities in the cardiovascular area (60%), and the use of drugs related to that area.
High blood pressure (HBP) 20 cases, diabetes mellitus (DM) 10 cases, stroke 5 cases, heart failure 2 cases, pacemaker 1 case, arrhythmia one case, dyslipidemia International Journal of Clinical Medicine

The Deterioration or Loss of the Baroreflexes
In 10 cases (24% of positive HUTs), we found damage to the baroreflexes, corroborated as orthostatic hypotension, without accompanying tachycardia [21] plus abnormalities in blood pressure response in the Valsalva Maneuver and in deep breathing test [22] [23].

Situational Syncope
We found two patients with situational syncope. Both males. One of them when coughing presented syncope with severe drop in BP and HR, consistent with his symptoms ("cough syncope"). However, his orthostatic HUT was negative.
The other case presented episodes of very prolonged laughter ("gelastic syncope"), with choking and syncope. His orthostatic HUT was positive (vasodilator).

Carotid Sinus Syncope
Carotid sinus compression was practiced in all patients 60 years of age or older, according to what international protocols dictate [11].
Compression was positive in 2 males (4%). Mean age 66 years. Both had a negative orthostatic HUT for vasovagal dysautonomia. They consulted for presenting dizziness or syncope when changes in posture of the head. This endorses the usefulness of using such compression in the study of syncope in older adults.
[11]. All three with failure in the baroreflexes and positive HUT for OH.

Parkinson's Disease
In one with recent Parkinson's (3 years). HUT was performed to rule out dysautonomia. He did not suffer from syncope or lipothymia. His HUT was negative.

Follow Up
This covers between 15 months and 7 years (X: 4.5 years). It allowed us to find causes that are unusual at younger ages: Use of hypotensive drugs (n: 8), one of them, added a diabetic autonomic neuropathy. Postprandial syncope (n: 4), post-stroke dizziness (n: 1). Arrhythmia (n: 1). Carotid sinus syndrome (n: 2).
Sleep apnea with hypersomnia (n: 1) and degenerative neurological diseases such as Parkinson's disease with dysautonomia (n: 3). The total for this type of unusual cause is 20 cases (38%).

Unexplained Cases
Despite follow-up and complementary examinations, there were 6 patients (11%), in whom we did not find associated factors that made them prone to syncope.
They all had a positive HUT. Three with OH and three with vasovagal syncope.
In three of them, syncope occurred only once.

Discussion
Approximately 50% of people present their first fainting, between 15 and 30 years of age [1], at that age, its frequency is usually double in women and neurally mediated syncope (VVS) predominates as the first cause [2] [3].
But up to 10% to 15% of the population would have it after the age of 65 [3].
In our patients over 50 years old, the relationship of sex is reversed, with the frequency being much higher in men (63% vs. 38%) than in women [27] [28].
The most important final event in HUT was orthostatic hypotension (46%).
Vasovagal syncope is relegated to second place with 29%. This supports the ob-

Hypotensive Drugs
Patients report that, when starting using a medication, fainting started or worsened, and stopped when they stopped using it. We can confirm it, by testing withdrawal or reducing doses. This occurred in 8 of 22 cases (36%) [8] [33] [34] [35] [36].
The effect of the sum of antihypertensive drugs in combination with psychotropic, anxiolytic, antidepressant drugs and the production of OH and syncope is clear [37].  [60]. It is due to an inadequate sympathetic response to splanchnic vasodilation produced during feeding.
Syncope due to compression of the carotid sinus, is usually mentioned as a cause of syncope in the elderly [11] [61] [62], but at least in our sample, was rare.
Three of them consulted for a single syncope and the others for a maximum of 2 or 3 episodes. We believe that in these patients, circumstances like ambient International Journal of Clinical Medicine heat, dehydration or prolonged standing came together at a certain moment: But during follow-up, they have not been repeated [63] [64] [65].
In this subgroup, it is mandatory to determine if they have a heart condition, since they have up to 30% more mortality than the population of the same age [2] [26]. So, our protocol includes carrying out a complete cardiological evaluation previous to HUT.

Study Limitations
First, it is difficult to obtain statistically valid conclusions due to the small number of patients studied in our sample. We understand that a greater sample is necessary in the future.
Second, we depend on the good memory of the patient or his relatives to recall that they are consulting for the first syncopal episode. In some cases, the patient, after a second interrogation, remembers having suffered episodes during childhood or adolescence (66).
Third, altough an exhaustive interrogation and pre-HUT exams, it is not always possible to completely rule out other causes such as drowsiness, vertigo, orthostatic dizziness or accidental falls.

In Sum
It is not common to begin with syncopes over age of 50.
Finding the ultimate cause for syncope in these patients can be difficult given the multiplicity of interacting factors. They are mainly male and exhibit different causes than those found at a young age.
Its study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, knowing the concomitant diseases and careful monitoring to get closer to the diagnosis. We observe the high frequency of orthostatic hypotension as a cause for syncope, which is attributable in many cases to advanced age, failure of baroreflexes, cardiovascular and neurological diseases, and polypharmacy [29] [66] [67].