Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: <=90 (n=6264); <=85 (n=6264); <=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure<=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure <=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of <=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of <=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels <=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure <=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

Late Results of Endoventricular Patch Plasty Repair in Akinetic and Dyskinetic Areas After Acute Myocardial Infarction

OBJECTIVE - To assess the surgical results of endoventricular patch plasty repair in akinetic and dyskinetic left ventricular areas. METHODS - We studied 52 patients who had undergone endoventricular patch plasty repair associated with myocardial revascularization. The preoperative functional class distribution was as follows: class I in 1 (1.9%) patient; class II in 2 (3.8%) patients; class III in 23 (44.2%) patients; and class IV in 26 (50%) patients. RESULTS - The immediate mortality rate was 7.6% (4 patients). The clinical outcome of 44 patients followed up within a mean postoperative time of 29±25 months was as follows: class I in 33 (75%) patients; class II in 7 (15.9%) patients; class III in 2 (4.5%) patients; and class IV in 2 (4.5%) patients. Comparison between pre- and postoperative catheterization in 21 patients showed that the ejection fraction increased from 46.3% to 51.3% (p=0. 17); the left ventricular systolic volume decreased from 76.4 mL to 57.5 mL, (p=0.078); and the left ventricular diastolic volume decreased from 141.2 mL to 105.8 mL (p=0.0 73). These findings showed the tendency toward improvement, but with nonsignificant results. CONCLUSION - The technique proved to be effective, to have a low mortality rate, to cause significant clinical improvement, an increase in ejection fraction, and a reduction in left ventricular volumes.

Improvement in left ventricular dysfunction after surgical correction of mitral regurgitation

OBJECTIVE: To evaluate whether left ventricular end-systolic (ESD) diameters £ 51mm in patients (pt) with severe chronic mitral regurgitation (MR) are predictors of a poor prognosis after mitral valve surgery (MVS). METHODS: Eleven pt (aged 36±13 years) were studied in the preoperative period (pre), median of 36 days; in the early postoperative period (post1), median of 9 days; and in the late postoperative period (post2), mean of 38.5±37.6 months. Clinical and echocardiographic data were gathered from each pt with MR and systolic diameter ³51mm (mean = 57±4mm) to evaluate the result of MVS. Ten patients were in NYHA Class III/IV. RESULTS: All but 2 pt improved in functional class. Two pt died from heart failure and infectious endocarditis 14 and 11 months, respectively, after valve replacement. According to ejection fraction (EF) in post2, we identified 2 groups: group 1 (n=6), whose EF decreased in post1, but increased in post2 (p=0.01) and group 2 (n=5), whose EF decreased progressively from post1 to post2 (p=0.10). All pt with symptoms lasting £ 48 months had improvement in EF in post2 (p=0.01). CONCLUSION: ESD ³51mm are not always associated with a poor prognosis after MVS in patients with MR. Symptoms lasting up to 48 months are associated with improvement in left ventricular function.

Effect of oscillatory breathing on the variability of the RR Intervals and its prognostic importance in individuals with left ventricular global systolic dysfunction

OBJECTIVE: To assess the effect of the oscillatory breathing on the variability of RR intervals (VRR) and on prognostic significance after one year follow-up in subjects with left ventricular global systolic dysfunction. METHODS: We studied 76 subjects, whose age ranged from 40 to 80 years, paired for age and gender, divided into two groups: group I - 34 healthy subjects; group II - 42 subjects with left ventricular global systolic dysfunction (ejection fraction < 0.40). The ECG signals were acquired during 600s in supine position, and analyzed the variation of the thoracic amplitude and the VRR. Clinical and V-RR variables were applied into a logistic multivariate model to foretell survival after one year follow-up. RESULTS: Oscillatory breathing was detected in 35.7% of subjects in vigil state of group II, with a concentration of the spectral power in the very low frequency band, and was independent of the presence of diabetes, functional class, ejection fraction, cause of ventricular dysfunction and survival after one year follow-up. In the logistic regression model, ejection fraction was the only independent variable to predict survival. CONCLUSION: 1) Oscillatory breathing pattern is frequent during wakefulness in the left ventricular global systolic dysfunction and concentrates spectral power in the very low band of V-RR; 2) it does not relate to severity and cause of left ventricular dysfunction; 3) ejection fraction is the only independent predictive variable for survival in this group of subjects.

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

Atrial Fibrillation Ablation in Systolic Dysfunction: Clinical and Echocardiographic Outcomes

Background:Heart failure and atrial fibrillation (AF) often coexist in a deleterious cycle.Objective:To evaluate the clinical and echocardiographic outcomes of patients with ventricular systolic dysfunction and AF treated with radiofrequency (RF) ablation.Methods:Patients with ventricular systolic dysfunction [ejection fraction (EF) <50%] and AF refractory to drug therapy underwent stepwise RF ablation in the same session with pulmonary vein isolation, ablation of AF nests and of residual atrial tachycardia, named "background tachycardia". Clinical (NYHA functional class) and echocardiographic (EF, left atrial diameter) data were compared (McNemar test and t test) before and after ablation.Results:31 patients (6 women, 25 men), aged 37 to 77 years (mean, 59.8±10.6), underwent RF ablation. The etiology was mainly idiopathic (19 p, 61%). During a mean follow-up of 20.3±17 months, 24 patients (77%) were in sinus rhythm, 11 (35%) being on amiodarone. Eight patients (26%) underwent more than one procedure (6 underwent 2 procedures, and 2 underwent 3 procedures). Significant NYHA functional class improvement was observed (pre-ablation: 2.23±0.56; postablation: 1.13±0.35; p<0.0001). The echocardiographic outcome also showed significant ventricular function improvement (EF pre: 44.68%±6.02%, post: 59%±13.2%, p=0.0005) and a significant left atrial diameter reduction (pre: 46.61±7.3 mm; post: 43.59±6.6 mm; p=0.026). No major complications occurred.Conclusion:Our findings suggest that AF ablation in patients with ventricular systolic dysfunction is a safe and highly effective procedure. Arrhythmia control has a great impact on ventricular function recovery and functional class improvement.

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy

Background:Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.Objective:To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.Methods:10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.Results:Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.Conclusion:An impairment of LA functions in Chagas cardiomyopathy was observed.

Diastolic Function in Paced Children with Cardiac Defects: Septum vs Apex

AbstractIn children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial.The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects.Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow‑up of 4.9 years.Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 ± 9.19 vs 83 ± 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E´ wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R2= 0.9849, p ≤ 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function.Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function.

Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation

Background:Primary graft dysfunction is the main cause of early mortality after heart transplantation. Mechanical circulatory support has been used to treat this syndrome.Objective:Describe the experience with extracorporeal membrane oxygenation to treat post-transplant primary cardiac graft dysfunction.Methods:Between January 2007 and December 2013, a total of 71 orthotopic heart transplantations were performed in patients with advanced heart failure. Eleven (15.5%) of these patients who presented primary graft dysfunction constituted the population of this study. Primary graft dysfunction manifested in our population as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe hemodynamic instability in the immediate postoperative period with severe cardiac dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia time was 151 ± 82 minutes. Once the diagnosis of primary graft dysfunction was established, we installed a mechanical circulatory support to stabilize the severe hemodynamic condition of the patients and followed their progression longitudinally.Results:The average duration of extracorporeal membrane oxygenation support was 76 ± 47.4 hours (range 32 to 144 hours). Weaning with cardiac recovery was successful in nine (81.8%) patients. However, two patients who presented cardiac recovery did not survive to hospital discharge.Conclusion:Mechanical circulatory support with central extracorporeal membrane oxygenation promoted cardiac recovery within a few days in most patients.

Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity

Abstract Background: Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation. Objective: This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals. Methods: Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student’s t-test, with a level of significance of 5%. Results: Obese subjects had lower values of SDNN (40.0 ± 18.0 ms vs. 70.0 ± 27.8 ms; p = 0.0004), RMSSD (23.7 ± 13.0 ms vs. 40.3 ± 22.4 ms; p = 0.0030), pNN50 (14.8 ± 10.4 % vs. 25.9 ± 7.2%; p = 0.0061) and HF (30.0 ± 17.5 Hz vs. 51.7 ± 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 ± 2.8 vs. 1.0 ± 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 ± 30.2 Hz vs. 40.9 ± 23.9 Hz; p = 0.9013). Conclusion: morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction.

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

Abstract Background: Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. Objective: To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Methods: Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. Results: The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Conclusion: Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.

Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

Abstract Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05). Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05). Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients

Background: Cerebral cholinergic transmission plays a key role in cognitive function and anticholinergic drugs are associated with impaired cognitive functions [1]. In the perioperative phase many substances with anticholinergic effects are administered and disturbed cholinergic transmission is a hypothetical cause of postoperative cognitive dysfunction (POCD). Serum anticholinergic activity (SAA; pmol/ml) may be measured as a summary marker of anticholinergic activity in an individual patient's blood. We hypothesised that an increase in SAA from preoperatively to one week postoperatively is associated with POCD in elderly patients. Methods: Thirty-two patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl) were investigated. Cognitive functions were measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 cognitive domains. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Results: 50% of the investigated patients developed POCD. There were no statistically significant differences between patients with and without POCD regarding age, education, baseline cognitive function, duration of anaesthesia, SAA preoperatively (median (range) 1.0 (0.3 to 5.0) vs 1.5 (0.4 to 5.0), SAA 7 days postoperatively (median (range) 1.3 (0.1 to 7.0) vs 1.4 (0.6 to 5.5) or changes in SAA (median (range) 0.1 (-1.6 to 2.2) vs 0.2 (-1.4 to 2.8). The variability of SAA in individual patients was considerable and marked changes in SAA between the two examinations were observed in some patients. However, there was no significant relationship between changes in SAA and changes in cognitive function. Conclusion: In this preliminary analysis of a small group of patients, changes in SAA in the perioperative phase were highly variable. SAA was not associated with POCD suggesting that POCD is not simply caused by anticholinergic medications administered in the perioperative phase. A further analysis of a larger group of patients is in progress.