The significance of amlodipine on autonomic nervous system adjustment (ANSA method): A new approach in the treatment of hypertension

Introduction. Cardiovascular autonomic modulation is altered in patients with essential hypertension. Objective To evaluate acute and long-term effects of amlodipine on cardiovascular autonomic function and haemodynamic status in patients with mild essential hypertension. Methods. Ninety patients (43 male, mean age 52.12 ±10.7) years with mild hypertension were tested before, 30 minutes after the first 5 mg oral dose of amlodipine and three weeks after monotherapy with amlodipine. A comprehensive study protocol was done including finger blood pressure variability (BPV) and heart rate variability (HRV) beat-to-beat analysis with impedance cardiography, ECG with software short-term HRV and nonlinear analysis, 24-hour Holter ECG monitoring with QT and HRV analysis, 24-hour blood pressure (BP) monitoring with systolic and diastolic BPV analysis, cardiovascular autonomic reflex tests, cold pressure test, mental stress test. The patients were also divided into sympathetic and parasympathetic groups, depending on predominance in short time spectral analysis of sympathovagal balance according to low frequency and high frequency values. Results. We confirmed a significant systolic and diastolic BP reduction, and a reduction of pulse pressure during day, night and early morning hours. The reduction of supraventricular and ventricular ectopic beats during the night was also achieved with therapy, but without statistical significance. The increment of sympathetic activity in early phase of amlodipine therapy was without statistical significance and persistence of sympathetic predominance after a few weeks of therapy detected based on the results of short-term spectral HRV analysis. All time domain parameters of long-term HRV analysis were decreased and low frequency amongst spectral parameters. Amlodipne reduced baroreflex sensitivity after three weeks of therapy, but increased it immediately after the administration of the first dose. Conclusion. The results of the study showed that amlodipine affected autonomic modulation as a shift to sympathetic hyperactivity, but without statistical significance. In the selected group of patients with vagal predominance in sympathovagal balance, amlodipine increased sympathetic and decreases vagal activity. Therefore we conclude that amlodipine mostly exerts impact on autonomic function modulation in patients with vagal predominance in resting state

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial

AIMS: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure. METHODS AND RESULTS: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001). CONCLUSION: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306

Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk

Introduction. The manifestations of autonomic nervous system (ANS) dysfunction in autoimmune diseases have been the subject of many studies. However, the published results pertaining to such research are controversial. Sudden cardiac death due to fatal arrhythmias is frequent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Objective. To analyze risk predictors of sudden cardiac death related to the degree of autonomic dysfunction. Methods. We performed cardiovascular ANS assessment in 90 patients in this case-controlled study, including 52 (6 male, 46 female) patients with SLE, 38 (6 male, 32 female) with RA and 41 (23 male, 17 female) healthy subjects. The methodology included a comprehensive ECG analysis (with Schiller software AT-10) of QTc interval, late potentials, short-term heart rate variability (HRV) and nonlinear HRV (Poincare plot) analysis; 24-hour Holter ECG monitoring with ECG QTc interval analysis, HRV analysis; 24-hour blood pressure monitoring with systolic and diastolic blood pressure variability; cardiovascular autonomic reflex tests (according to Ewing). Vagal dysfunction was established by performing 3 tests: Valsalva maneuver, deep breathing test and heart rate response to standing test. Dysfunction of the sympathetic nervous system was examined by applying 2 tests: blood pressure response to standing and handgrip test. Results. In all cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the healthy subjects. Severe autonomic dysfunction was more common in RA. QTc interval was more prolonged in patients with SLE. Both diseases were associated with depressed heart rate variability compared to controls, the reduction being greater in RA patients. In the patients with SLE, autonomic dysfunction is predominantly with higher sympathetic activity while in RA vagal predominance is evident. Conclusion. SLE and RA are associated with severe autonomic dysfunction and the presence of significant risk predictors related to the onset of sudden cardiac death

SUMMARY

Introduction Cardiovascular autonomic modulation is altered in patients with essential hypertension. Objective To evaluate acute and long-term effects of amlodipine on cardiovascular autonomic function and haemodynamic status in patients with mild essential hypertension. Methods Ninety patients (43 male, mean age 52.12 ±10.7) years with mild hypertension were tested before, 30 minutes after the first 5 mg oral dose of amlodipine and three weeks after monotherapy with amlodipine. A comprehensiv

Prognostic value of Poincare plot as nonlinear parameter of chaos theory in patients with myocardial infarction

Introduction: There are different proofs about association of autonomic nervous system dysfunction, especially nonlinear parameters, with higher mortality after myocardial infarction. Objective The objective of the study was to determine predictive value of Poincare plot as nonlinear parameter and other significant standard risk predictors: ejection fraction of the left ventricle, late potentials, ventricular arrhythmias, and QT interval. Method The study included 1081 patients with mean follow up of 28 months (ranging fom 0-80 months). End-point of the study was cardiovascular mortality. The following diagnostic methods were used during the second week: ECG with commercial software Schiller AT-10: short time spectral analysis of RR variability with analysis of Poincare plot as nonlinear parameter and late potentials; 24-hour ambulatory ECG monitoring: QT interval, RR interval, QT/RR slope, ventricular arrhythmias (Lown &gt;II); echocardiography examinations: systolic disorder (defined as EF&lt;40 %). Results There were 103 (9.52%) cardiovascular deaths during the follow-up. In univariate analysis, the following parameters were significantly correlated with mortality: mean RR interval &lt; 800 ms, QT and RR interval space relationship as mean RR interval &lt; 800 ms and QT interval &gt; 350 ms, positive late potentials, systolic dysfunction, Poincare plot as a point, ventricular arrhythmias (Lown &gt; II). In multivariate analysis, the significant risk predictors were: Poincare plot as a point and mean RR interval lower than 800 ms. Conclusion Mean RR interval lower than 800 ms and nonlinear and space presentation of RR interval as a point Poincare plot were multivariate risk predictors

Early risk predictors of sudden cardiac death after myocardial infarction: Results of follow up of 881 patients

Introduction: It has been shown that depolarization disorders, autonomic dysfunction, and systolic dysfunction of the left ventricle are associated with sudden cardiac death after myocardial infarction. Objective: The Objective of study was to examine the prognostic value of the most important predictors in the first week after myocardial infarction. Method: Study included 881 patients who were followed up from 1 to 60 months. During the first week after myocardial infarction, following examination were performed: ECG with standard leads and X, Y, Z orthogonal leads, vectorcardiogram, QT interval, late potentials, short-time spectral analysis of RR variability, nonlinear (Poincare plot) analysis and echocardiogram. Results: In univariate analysis, the following parameters measured on the first day were important predictors of sudden cardiac death: lower LF/HF ratio(&lt;1.5) (p=0.000), T wave inversion in X lead (p=0.000), high P wave in D2 lead (p=0.030), and diminished systolic function (p=0.000). In multivariate analysis, the following parameters were significant risk predictors: T wave inversion in X lead, lower LF/HF ratio, positive late potentials and the left ventricle systolic dysfunction. Conclusion: The parameters of the left ventricle systolic dysfunction with sympathicovagal imbalance and electric instability are the key risk predictors in the first few days after myocardial infarction

Brugada syndrome: Case report

Introduction. Brugada syndrome is an arrhythmogenic disease characterized by coved ST segment elevation and J point elevation of at least 2 mm in at least two of the right precordial ECG leads (V1-3) and ventricular arrhythmias, syncope, and sudden death. Risk stratifications of patients with Brugada electrocardiogram are being strongly debated. Case Outline. A 23-year-old man was admitted to the Coronary Care Unit of the Clinical Centre “Bežanijska kosa” due to weakness, fatigue and chest discomfort. The patient suffered from fainting and palpitations. There was a family history of paternal sudden death at 36 years. Electrocardiogram showed a coved ST segment elevation of 4 mm in leads V1 and V2, recognised as spontaneous type 1 Brugada pattern. Laboratory investigations revealed normal serum cardiac troponin T and serum potassium, and absence of inflammation signs. Echocardiographic finding was normal, except for a mild enlargement of the right atrium and ventricle. The diagnosis of Brugada syndrome was made by Brugada-type 1 electrocardiogram and the family history of sudden death &lt;45 years. The patient was considered as a high risk, because of pre-syncope and palpitations. He underwent ICD implantation (Medtronic MaximoVR7232Cx) using the standard procedure. After implantation, noninvasive electrophysiology study was done and demonstrated inducible VF that was interrupted with the second 35 J DC shock. The patient was discharged in stable condition with beta-blocker therapy. After a year of pacemaker check-ups, there were no either VT/ VF events or ICD therapy. Conclusion. Clinical presentation is the most important parameter in risk stratification of patients with Brugada electrocardiogram and Brugada syndrome

Cervical lymphodenopathy: A single presentation of sarcoidosis

Background. Sarcoidosis is a chronic inflammatory disease, commonly found in lungs and hilar lymph nodes, but multiple organs could be involved. The diagnosis is based on specific pathohistology which should be always combined with clinical, radiological and laboratory findings. Case report. A patient initially presented with pneumonia, and treated with antibiotics, but with the general symptoms that persisted despite radiological resolution of lung infiltration was reported. The further diagnostic procedures revealed the presence of sarcoid granulomas in cervical lymph nodes. The peripheral lymph nodes are often affected in the early course of the disease, but it is difficult to distinguish if the illness is a sarcoid reaction to lung infection or a acute onset of sarcoidosis. Conclusion. The detection of sarcoid granulomas in cervical lymph nodes should be precisely analyzed for the presence of sarcoidal changes in other tissues, primarily in the lungs tissue. Early diagnosis of lung sarcoidosis is significant, especially in the light of the fact that the latest studies point out that the prednisone therapy, started immediately after the diagnosis has been made, renders positive effects also in asympthomatic patients in II and III phase of the disease

Preoperative echocardiographic parameters influencing quality of life five years after coronary artery bypass graft surgery

Background/Aim. Factors associated with mortality and morbidity following coronary artery bypass graft surgery have been well defined and the Parsonnet score is widely used in mortality prediction. The evaluation of quality of life has not been still implemented in everyday work and preoperative echocardiographic factors affecting the quality of life in patients undergoing coronary artery bypass graft surgery have been poorly documented. The aim of this study was to evaluate echocardiographic parameters influencing quality of life following coronary artery bypass graft surgery and its correlation with widely used Parsonnet score. Methods. A total of 449 consecutive patients with myocardial revascularization, operated during 1999 and 2000 were enrolled in this retrospective-prospective study. The patients with comorbidities were excluded as well as those with in complete myocardial revascularization. A group of 180 patients who accepted to participate in quality of life evaluation was followed for 60 months. The quality of life was evaluated using a questionnaire SF-36. Results. The mean patients' age was 57.8 ± 7.8 years, 79.4% were males. A 5-year survival was 84.2%. The mean number of risk factors was 3.4 ± 1.0. Most of the patients were in New York Heart Associatiation (NYHA) II class (104 of them or 59.4%), 61 of them (34.9%) in NYHA III class and only 10 patients or 5.7% of them were in NYHA IV class. The mean End-Diastolic Diameter (EDD) was 55.3 ± 5.6 mm, mean End- Systolic Diameter (ESD) 38.7 ± 5.6 mm and mean ejection fraction (EF) 51.7 ± 9.6%. Left atrium dilatation (p &lt; 0.001), as well as left ventricle dilatation (p &lt; 0.001), low left ventricle ejection fraction (p &lt; 0.001), multisegmental disorders of contractility (p &lt; 0.001), and severe mitral regurgitation (p &lt; 0.001) were in negative correlation with almost all dimensions of quality of life. ROC analysis showed that left ventricle EDD of 54.5 mm can be used as good cut-off value for prediction of optimal quality of life, with sensitivity of 57% and specificity of 70% (RR = 1.386), left ventricle ESD of 37.5 mm with sensitivity of 65% and specificity of 57% (RR = 0.855) and left ventricle EF of 50% with sensitivity of 61% and specificity of 70% (RR = 0.916). Conclusion. Echocardiographic parameters, that can easily be obtained preoperatively, have strong predictive value not only in postoperative survival, but also in determination of the quality of life of the patients five years after coronary artery bypass graft surgery