Simona Maule

Orthostatic hypotension: evaluation and treatment.

Orthostatic hypotension (OH) may be dependent upon various neurogenic and non-neurogenic disorders and conditions. Neurogenic causes include the main autonomic failure syndromes, primary (multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinsons disease) and secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). Non-neurogenic causes of OH include cardiac impairment, fluid and electrolyte loss, vasodilatation, and old age. A number of drugs may also cause OH, through their vasoactive action or by interfering with the autonomic nervous system. Symptoms of OH are debilitating, often confining patients to bed, and longitudinal studies have shown that OH increases the risk of stroke, myocardial ischemia and mortality. The therapeutic goal is to decrease the incidence and severity of postural symptoms, rather than restore normotension. In non-neurogenic OH, treatment of the underlying cause may be curative. In neurogenic OH a combination of non-pharmacological and pharmacological measures is often needed. Patient education and non-pharmacological measures represent the first step; among these interventions, fluid repletion and physical countermanoeuvres have been proven very effective. Pharmacological treatment comprises a number of agents acting on blood vessels, on blood volume or with other pressor mechanisms. The drugs most currently used are fludrocortisone and midodrine. Fludrocortisone expands the extravascular body fluid volume and improves alpha-adrenergic sensitivity. Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction. Despite the wide use of these drugs, multicentre, randomised and controlled studies for the treatment of OH are still scarce and limited to few agents and groups of patients. Pharmacological management of OH substantially improves the quality of life of patients, although it may be problematic. The development of supine hypertension and subsequent congestive heart failure should be avoided, especially in those patients with a pre-existing cardiovascular risk, such as in diabetes or ischemic heart disease.

The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects

Cardiovascular responses to altitude have been studied on well-trained young subjects, generally at high altitudes (>4000 m). Less known are the effects of exposure to lower altitudes, easily reached by the general population. The aim of the study was to evaluate the effects of exposure to a moderate altitude (2950 m) on heart rate (HR), blood pressure (BP) profile, and cardiovascular autonomic function, and their correlation with hemoglobin oxygen saturation (HbO2S), in untrained subjects of a wide age range. Twenty-seven healthy normotensive subjects (age range 6–83; 8 children, 9 adults, and 10 elderly subjects) underwent a battery of noninvasive cardiovascular reflex tests and 24-h ambulatory BP monitoring. Corrected QT interval was also calculated. HbO2S was measured with a transcutaneous oxymeter. All measurements were performed at about 200 m (s.l.) and repeated at 2950 m. 24-h HR and systolic/diastolic BP mean values increased at 2950 m in children (% change respectively: 6.4±6.4, p<0.05; 6.5±4.0/13.5±6.9, p<0.05), adults (4.9±8.1, NS; 6.0±5.1/8.1±5.8, p<0.05), and elderly subjects (7.2±4.8, p<0.05; 5.1±2.3/2.8±4.1, p<0.05 for systolic BP only). Standard deviation of BP mean values increased during night-time in the adult group (p<0.05). All subjects scored normal cardiovascular test results and no differences were observed after exposure to 2950m, at both 1 hour and 24 hours from arrival. After exposure to altitude, HbO2S decreased significantly in the three groups, both on arrival and after 24 hours. No correlation was found between changes in HbO2S and BP/HR responses, and cardiovascular test results. In conclusion, exposure to moderate altitudes, easily and often reached by the general population, causes a small but significant increase in BP and HR in healthy untrained subjects of a wide age range (6–83 years). Some physiological factors (eg, lower environmental temperature and lifestyle modification) together with hypoxia, possibly more than altered cardiovascular reactivity, seem responsible for this cardiovascular change. In terms of end-organ damage, the clinical relevance of this increase in BP and BP variability for repeated exposure is not known.

Prolonged QT interval and reduced heart rate variability in patients with uncomplicated essential hypertension.

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Heart rate variability (HRV) is both an index of autonomic function and an important prognostic factor in several diseases. The aim of the present study was to evaluate the relation between a prolonged QT interval and autonomic nervous system function in patients with untreated uncomplicated essential hypertension. Two hundred and fifteen untreated patients with essential hypertension underwent a Holter ECG equipped with software dedicated to HRV and QT analyses. Nine percent of the patients showed a corrected QT (QTc) ≥440 ms. The HRV indexes in the time domain (SDNN, SDNN index, RMSSD, and pNN50) were significantly reduced in the patients with a prolonged QTc compared to those with a normal QTc (SDNN 24 h: 126.4±29.9 vs. 143.9±35.4 ms, p=0.02; SDNN index [nighttime]: 85.9±32.4 vs. 115.5±36.7 ms, p=0.0006; RMSSD 24 h: 22.2±7.7 vs. 31.2±13.0 ms, p=0.0007; pNN50 24 h: 4.4±4.9 vs. 9.7±8.4%, p=0.0006). The linear correlation analysis between QTc length and HRV parameters showed a significant negative correlation with all the time-domain indexes. Such a correlation was maintained for RMSSD 24 h, pNN50 24 h and SDNN index (nighttime) after correction for gender and age. The present study shows that, even prior to the development of cardiac hypertensive disease, a prolongation of the QTc and a reduced HRV, both markers of cardiovascular risk, coexist in a proportion of patients with untreated essential hypertension. Further studies are warranted to evaluate whether the combination of such markers can identify hypertensive patients at risk for life-threatening arrhythmias and sudden death.

Autonomic neuropathy and QT interval in hemodialysed patients.

Abstract.Background QT interval prolongation increases the risk of ventricular arrhythmias and sudden death in diabetic autonomic neuropathy and ischemic heart disease. In end–stage renal disease (ESRD), the effects of hemodialysis on QT interval are diverse and the influence of autonomic neuropathy has yet to be clearly defined.MethodsSixty–nine ERSD patients (age 64 ± 14) were studied. Prior to the dialysis session, patients underwent four standard autonomic cardiovascular tests; before and after the dialysis session, a 12–lead ECG was recorded. Corrected QT intervals (QTc) were measured and QT dispersion (QTd) was calculated. Twelve subjects (age 59 ± 6) with normal renal function served as control group.ResultsCompared to controls, ESRD patients showed a longer QTc (434 ± 26 vs 414 ± 28ms; p = 0.016) and a similar QTd (35 ± 13 vs 37 ± 14ms; p = 0.54).QTc was > 440ms in 33.3% of the patients. No difference in the prevalence or score of autonomic neuropathy was observed between the subgroups with and without a prolonged QTc. After the hemodialysis session, QTc increased in 56% and decreased in 43% of the patients, and QTd increased in 45 % and decreased in 55% of the patients. QTc and QTd changes were not related to the presence of autonomic neuropathy.ConclusionsA large variability in QTc and QTd response was observed after hemodialysis. Autonomic neuropathy did not contribute to QTc and QTd length, nor to QTc and QTd change after dialysis.

The influence of autonomic neuropathy on hypotension during hemodialysis.

Abstract Many patients with chronic renal failure experience profound hypotension during hemodialysis. This phenomenon may be caused by hypovolemia, autonomic or cardiac dysfunction, vascular resistance defects or vasoactive substances such as nitric oxide or adrenomedullin. The aim of the study was to evaluate the influence of autonomic neuropathy on the occurrence of hypotension during hemodialysis. Fifty-three patients with chronic renal failure on maintenance hemodialysis underwent a standard battery of cardiovascular tests for the diagnosis of autonomic neuropathy. The study population was then divided into two groups, with (AN+) and without (AN−) autonomic neuropathy. Blood pressure (BP) was recorded before, during and after hemodialysis for 10 consecutive dialysis sessions and the mean value was calculated. Results Of the patients, 38 % were AN+. During hemodialysis, systolic BP was lower in AN+ than in AN− patients at the third hour (110.0 ± 17.5 vs 128.0 ± 26.2; p = 0.049). Systolic BP reduction during hemodialysis was greater in AN+ than AN− patients (−21.2 ± 10.9 vs −13.5 ± 10.6 % change, p = 0.013). Conclusion The presence of autonomic neuropathy is associated with a more severe BP fall during hemodialysis. Routine evaluation of autonomic function may be helpful in defining patients at risk for dialysis-induced hypotension.

QT interval in patients with primary aldosteronism and low-renin essential hypertension.

Introduction QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). Methods Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. Results The QTc was longer in primary aldosteronism (434 ± 23 ms) and LREH (430 ± 18 ms) compared with essential hypertension (419 ± 22 ms) and healthy controls (412 ± 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. Conclusions We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH.

Cognitive Decline and Low Blood Pressure: The Other Side of the Coin

Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.

Relationship between QT interval and cardiovascular risk factors in healthy young subjects

A prolongation of QT interval increases the risk for coronary heart disease, ventricular arrhythmias, and sudden death in diabetic patients, after myocardial infarction, and in the elderly. An association between QT prolongation and cardiovascular risk factors has been demonstrated in middle-aged and elderly subjects. Aims of this study were to evaluate the prevalence of a prolonged corrected QT interval (QTc) in a healthy young population (n=170, age 22–25 years, 84 males) and to investigate the association of QTc and QT dispersion (QTd) with cardiovascular risk factors (body mass index, blood pressure, fasting blood glucose and cholesterol, smoking habits, and hypertensive familiarity). A prolonged QTc was observed in 10% of female and 5% of male subjects; in multiple regression analysis, QTc showed a significant positive relationship with blood glucose in females (P=0.04) and systolic blood pressure in male subjects (P=0.03), while QTd was not significantly related with any of the factors. In conclusion, the association between QTc length, glucose levels, and blood pressure is present also in young healthy subjects. QT measurement may represent a useful marker in the screening of young subjects for cardiovascular prevention.

Drugs and Orthostatic Hypotension: Evidence from Literature

Orthostatic hypotension is defined as the reduction of systolic blood pressure of at least 20 mmHg or the dropping of diastolic blood pressure of at least 10 mmHg within 3 minutes of standing compared to baseline values. It can be divided into neurogenic and non neurogenic forms. Neurogenic forms are caused by a primitive damage to autonomic nervous system, while drugs are the most common cause of non neurogenic orthostatic hypotension; they may also complicate or aggravate neurogenic forms. Many drugs can determine orthostatic hypotension, including both cardiovascular drugs and therapies used for neurological and psychiatric disorders. This effect is furthermore enhanced by multiple pharmacological treatments. It is important for the clinician to know the potential hazard of orthostatic hypotension, in order to avoid syncope, falls, hypoperfusion symptoms, excess of mortality and loss of compliance to treatment.

Postprandial hypotension treated with acarbose in a patient with type 1 diabetes mellitus.

Treatment of postprandial hypotension (PPH) is often unsuccessful. We report a case of a type 1 diabetic patient suffering from severely symptomatic PPH. The patient was treated with acarbose and showed definite improvement of both glycemic control and PPH.