Clinical trial NCT03209141: Screening of Diastolic Dysfunction With Impedance Cardiography in Hypertensive Patients
Official title: Impedance Cardiography in the Evaluation of Left Ventricular Diastolic Dysfunction in Patients With Arterial Hypertension Study (IMPEDDANS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension
Diastolic Dysfunction
Keywords: hypertension
Diastolic Dysfunction
impedance cardiography
echocardiography
Lead sponsor: Centro Hospitalar de Lisboa Central
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with arterial hypertension attending the outpatient clinic consultation

Brief summary: Arterial hypertension (AHT) is responsible for important morbidity and mortality. The cardiac repercussion of AHT is usually assessed by electrocardiography and echocardiography, time-consuming, technically demanding examinations that require experienced operators, which limits their use for screening diastolic dysfunction. Alternative tools for the screening of diastolic function in hypertensive patients are needed. Impedance cardiography (IC) is presently used in the study of AHT and in the optimization of antihypertensive therapy. It seems an attractive and economical option to change the clinical approach for screening; however, its validation in well-defined populations is required to sustain its use in clinical practice. The IMPEDDANS study aims to validate IC for screening left ventricular diastolic dysfunction in outclinic patients with AHT, using functional echocardiography as the clinical standard. Descriptive and analytical study with analysis of the agreement between the diagnosis of diastolic dysfunction and its degree, as well as the parameters obtained by impedance cardiography and echocardiography in patients with AHT.

Detailed description: BACKGROUND. Impedance cardiography (IC) is a complementary diagnostic test used in the study of arterial hypertension (AHT) and in the optimization of antihypertensive therapy. It is easy-to-execute, non-operator-dependent and cost-effective. It analyses and registers hemodynamic changes through the measurement of electrical resistance changes in the thorax and translates them graphically as impedance and electrocardiogram waveforms. IC has evolved in recent years, making it an attractive and economical tool, particularly in screening settings and there is extensive published literature on its usefulness. More widespread use of IC has been limited due to limitations of the studies, mostly cross-sectional, with small samples, recruiting hemodynamically stable patients and providing inconsistent estimates of accuracy and reproducibility in different settings.

AHT is responsible for high morbidity and mortality. In Portugal, according to PHYSA study, has overall prevalence of hypertension, in 2014, of 42.2% (44.4% in men, 40.2% in women). The progression of hypertensive heart disease involves myocardial fibrosis and changes in left ventricular geometry that precedes functional changes. Diastolic dysfunction is part of this continuum, and despite the growing recognition of its importance, it is generally undervalued because of the difficulty in its diagnosis and the absence of effective therapies. This reinforces the importance of finding alternative tests that provide important information for an initial assessment of diastolic function in hypertensive patients.

This study intends to define the importance and usefulness of IC in the evaluation of LV diastolic dysfunction in patients with AHT.

METHODS. Study Design. This is a validation study of a diagnostic method used in a new context, comparing it with the diagnostic method currently used for this effect in usual clinical practice. Its purpose is to determine the positive predictive value, negative predictive value, sensitivity and specificity of the presence of the D wave, the isovolumetric relaxation time, the systolic time ratio (STR) and thoracic fluid content (TFC) by IC, for the diagnosis of LV diastolic dysfunction (LVDD). To study the relationship between LV geometry, hemodynamic profile, diastolic dysfunction and its degree (confirmed by echocardiography) in hypertensive patients with diastolic dysfunction. We chose to perform a concordance study between IC and echocardiography, the validated , non-invasive test used for the clinical diagnosis of LVDD as well as for the characterization of hypertensive cardiopathy.

To calculate the sample size we considered the primary endpoint (concordance of the diagnosis of diastolic dysfunction between IC and echocardiography). Thus, considering a hypothesized positive predictive value of 70 ± 5% of the parameters obtained by IC, 77 individuals are estimated to be able to verify the expected positive predictive value with 95% confidence. Since the prevalence of diastolic dysfunction in patients with AHT estimated to be approximately 50% in most studies, the sample size is doubled for 154 hypertensive patients.

Evaluation. Participants will be systematically assessed by IC and echocardiography, with a maximum interval of 8 days between them, to obtain the parameters to be used in the validation and concordance studies. To ensure that both tests are performed under similar conditions, evaluations matching variations greater than 10% in BP or variations in excess of 5% in HR will not be considered. These patients should, if possible, repeat one of the exams. If they maintain variations greater than those defined, they should be excluded from the study.

Baseline Data. Ambulatory clinic protocol for patients followed for AHT require clinical evaluation, blood test, electrocardiogram and, eventually, 24 hours ambulatory blood pressure monitoring (AMBP). Data regarding the comorbidities and pharmacotherapy will be collected. Anthropometric data regarding adiposity and vital signs will be registed and body mass index calculated as weight (kg) divided by height (m) squared. Blood pressure will be measured in a quiet room with semiautomatic device (Omron HEM-907XL, Omron Healthcare, Bannockburn, Illinois, USA) with an appropriate cuff according with the established recommendations. If necessary 24 hours ABPM will be performed using an ABPM device - Spacelabs model 90207 (Issaquah, Washington, USA) also according with current guidelines. Electrocardiogram will be performed per institutional protocol with a Page Writer TC 30, Philips, Eindhoven, Netherlands. The analytical screening evaluation includes complete blood count, haematocrit, urinalysis, urine microalbumin, serum sodium, potassium, creatinine (estimated or measured glomerular filtration rate \[GFR\]), and calcium, uric acid, glycated haemoglobin, lipid profile following a 9- to 12-hour fast (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), thyroid-stimulating hormone and brain natriuretic peptide.

Impedance Cardiography. Impedance cardiography will be carried out in a single centre by a cardiopneumology technician with Niccomo continuous cardiac output monitor (Medis, GmbH, Ilmenau, Germany). This equipment uses the technique of four electrodes, two of current application and two others that detect the changes of voltage. As the current amplitude is constant, the voltage detected is proportional to the tissue impedance. Patients must present with fasting of 6 hours but must take their antihypertensive drugs and the examination is carried out in 4 phases after an initial 5 minutes hemodynamic stabilization period: 1. supine position I - 20 minutes continuous recording; 2. 70º orthostatism -with the help of the tilting table for 10 min in continuous recording; 3. tilt-back at 0º; 4. supine position II - 10 min continuous recording. The examination is interrupted if there is syncope or pre-syncope; dizziness, nausea and malaise associated with poorly tolerated hypotension and / or bradycardia; pain / precordial discomfort; ECG ST segment changes; Systolic blood pressure \> 210mmHg.

Transthoracic Echocardiography. Transthoracic echocardiography will be performed in Vivid E9 and S5 devices (GE Healthcare, Chicago, Illinois, USA) by experienced cardiologists. The exam will be held in the echocardiography laboratories of two reference centers. To ensure uniformity of evaluation and correct evaluation all exams will be reviewed by a second cardiologist with experience in the technic. In order to define and grade diastolic dysfunction will be recorded left atrium volume index, the velocities E, A, septal e´, lateral e´, deceleration time (DT), isovolumetric relaxation time (IRVT), atrial reverse velocity (Ar) and E/A ratio variation with Valsalva maneuver (last two will only valued if the patient cooperates and if the images obtained have the necessary quality for analysis) as recommended by 2009 guidelines. Left ventricular geometry will be defined accordingly with international recommendations.

Analytic Statistics. The diagnostic validity parameters will be calculated with 95% confidence intervals, using logistic regression models. The positive and negative predictive values will be calculated and the sensitivity and specificity will be estimated; receiver-operator curves (ROC) will also be analysed, with the calculation of the area under the curve. Diagnostic models with more than one parameter will be tested, using multivariable analysis, logistic and linear regression. For the analysis of agreement between the parameters obtained by ICG and echocardiography, the Bland-Altman method will be used with STATA® and R-project® software.

Eligibility criteria: Inclusion Criteria:

* grade 2 or 3 hypertension (systolic blood pressure ≥ 160 mmHg and/or with diastolic blood pressure values ≥ 100 mmHg) and/or with resistant hypertension (as defined by European Society of Cardiology

Exclusion Criteria:

* pregnancy,
* height less than 120 cm or more than 230 cm,
* weight less than 30 kg or greater than 155 kg,
* heart failure II-IV NYHA,
* heart rate (HR) less than 50 bpm or greater than 110 bpm,
* atrial fibrillation or flutter,
* \> 3 premature ventricular contractions per hour,
* complete left bundle branch or atrioventricular block,
* severe valvulopathies,
* constrictive pericarditis,
* hypertrophic and restrictive cardiomyopathy,
* prior history of ischemic heart disease and/or segmental kinetics alterations assessed by echocardiography,
* left ejection fraction \< 50%,
* poor echocardiographic window ,
* pacemaker.

Primary outcomes:
measure: Predictive value of impedance cardiography to identify diastolic dysfunction
timeFrame: Less than 10 days between measurements
measure: Area under the curve (AUC)
timeFrame: Less than 10 days between measurements
Secondary outcomes:
measure: Negative predictive value of impedance cardiography to identify diastolic dysfunction
timeFrame: Less than 10 days between measurements
Other outcomes:
Locations:
city: Lisboa
country: Portugal
facility: Consulta de Hipertensão Arterial, UF Medicina 1.4 do Hospital São José, Centro Hospitalar de Lisboa Central
city: Lisboa
country: Portugal
facility: Consulta de Risco Vascular da Unidade Funcional Medicina 1.2, Hospital São José, Centro Hospitalar de Lisboa Central
city: Lisboa
country: Portugal
facility: Núcleo de Hipertensão Arterial, Consulta de Medicina do Hospital de Santa Marta, Centro Hospitalar de Lisboa Central
Study officials:
affiliation: Centro Hospitalar de Lisboa Central
name: Rodrigo N Leão, MD
role: PRINCIPAL_INVESTIGATOR
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