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PubMed1992

An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study)

Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QTc = QT/square root of RR) proposed in 1920 by Bazett. The QTc formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QTc and linear corrected QT (QTLC). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Heart rate and heart rate variability changes induced by right atrial pacing.

This research was conducted to determine (1) whether heart rate and R-R interval variability are modified by atrial pacing, and (2) whether these changes (if they do occur) are related to the inducibility of tachyarrhythmias during electrophysiological studies. We studied 42 patients who were referred for electrophysiological evaluation of supraventricular (n = 16) or ventricular arrhythmias (n = 26). The patients studied for the evaluation of ventricular arrhythmias had structural and functional cardiac damage. The patients evaluated because of supraventricular arrhythmias had normal ejection fraction and on structural cardiac damage. In these patients a significant decrease in R-R interval (P = 0.0002) and in its standard deviation (P < 0.005) was observed following atrial pacing. No significant heart rate or R-R interval standard deviation change was observed after pacing in the patients with structural heart disease. The heart rate or R-R interval variability changes did not allow us to discriminate the patients with inducible ventricular arrhythmias from those without such arrhythmias. We conclude that right atrial pacing induces a heart rate increase and R-R variability decrease in patients without heart disease. In patients with cardiac damage the responses are blunted, and do not permit the identification of patients who have ventricular arrhythmias inducible by means of electrophysiological studies.

Adult↗
PubMed1984

Heart rate discrimination and heart rate control: a test of Brener's theory.

Three experiments were conducted to examine predictions from Brener's theory regarding the relationship between autonomic discrimination and autonomic control. Experiment 1 examined the possibility that training subjects to discriminate their heart rates would enhance their skill at controlling that response. Twenty subjects participated in two sessions during which one group of 10 subjects received training (knowledge of results) on the Ashton discrimination technique. The second group performed the discrimination task but received no training. All subjects then took part in a third session of heart rate (HR) control (both increase and decrease) where half of each of the aforementioned groups received feedback during the control task, while the other half performed the HR control task without feedback. Results indicated that for the control of both HR increases and decreases, there was no significant difference between those subjects trained to discriminate their HR, and those who had received no training to discriminate HR. The second experiment investigated the hypothesis that training subjects with feedback to control their HR would enhance their capacity to discriminate their heart activity. Ten subjects participated in two sessions of HR control during which half the subjects received feedback training to increase HR. During a third session, all subjects underwent a test of discrimination ability using the Ashton technique, and no knowledge of results regarding performance was provided. Results confirmed the hypothesis. The final experiment in the series investigated the discrimination/control relationship within a problem-solving framework and used 20 subjects. Results confirmed the hypothesis that subjects forewarned at the time of discrimination training that a heart rate control task was to follow would perform better than 10 subjects receiving no forewarning of the task objective. This effect took place independently of cardiac discrimination ability. A second finding from this experiment was that subjects trained to discriminate heart rate were better able to increase heart rate than untrained subjects. This result contradicts that of Experiment 1, and reasons for this anomaly are discussed in detail.

Adolescent↗
PubMed1996

To what extent does a given heart rate correlate with following heart rates in the developing human fetus?

To quantitatively determine the extent to which a given heart rate correlates with the following heart rate(s) at any gestational age, we studied 181 uncomplicated human fetuses between 23 and 41 weeks gestation. A continuous 90-120 min observation was made for each case using external Doppler-ultrasound cardiotocography. For every individual fetal heart rate dataset, 'probability distribution matrices' were calculated with fetal heart rates (termed FHRs) at 1-beat/min (bpm) intervals, and the beat-to-beat(s) difference (termed DFHRn: 1 < or = n < or = 1000), also at 1-bpm intervals arranged in rows and columns, respectively, with probability in each element. Using 'piecewise linear regression', (1) the difference between the DFHR1 (n = 1) probability distribution matrix as the 'control' and a given DFHRn (n > or = 2) probability matrix as the 'variable', was analyzed to obtain the statistically critical point(s) (termed 'beat-delay' in beats) for each fetus, and (2) a scattergram of 'beat-delay' vs. gestational age-group, made from all fetuses studied, was analyzed to reveal any critical age(s) in gestation. One statistically significant point was evident at 28-29 weeks gestation. During the period prior to the critical point, a linear decrement in 'beat-delay' with 21 beats (mean) at 23-25 weeks to 11 beats at 28-29 weeks gestation was noted, suggesting that the conduction system-oriented heart beat gradually comes under functional control of the autonomic nervous system as well as under possible regulation by the maturating medulla oblongata. From the critical point, through to term, there was no significant change in 'beat-delay' ranging from 7-11 beats, thereby implying that the fetal heart rate becomes stabilized as a result of the control rendered by the more developed autonomic nervous system function. Whether or not brain function cephalad to the medulla oblongata actually participates in this phenomenon remains to be elucidated.

Embryonic and Fetal Development↗
PubMed2004

The expanding national burden of heart failure in the United States: the influence of heart failure in women.

BACKGROUND: Although some studies have shown that hospital admissions for heart failure doubled between 1973 and 1995, other data suggest that the heart failure hospitalization epidemic has stabilized in the United States. We sought to describe trends in heart failure hospitalizations over the past decade using data from the National Hospital Discharge Survey (NHDS). METHODS: The NHDS provides annual estimates of hospitalization discharges from a sample of hospitals in the United States. We combined the heart failure hospitalization frequencies with census estimates to calculate age and gender-specific annual hospitalization rates. RESULTS: Hospitalizations with a primary diagnosis of heart failure among adults (age > or =35) increased from 810,624 in 1990 to 989,500 in 1995 (annual increase 36,088, R2 = 0.816, P =.014), and to 1,088,349 in 1999 (annual increase 31,091, R2 = 0.780, P =.047). The age-adjusted hospitalization rate (per 1000 persons) increased from 7.186 in 1990 to 8.554 in 1999 for women (annual increase 0.14/year, R2 = 0.731, P =.002) and from 6.892 in 1990 to 7.372 in 1999 for men (annual increase 0.011/year, R2 = 0.008, P = 0.80). For women, the annual hospitalization rate increased from 1990 to 1999 in each age group (35-64, 65-74, 75-84, and > or =85), while the age-specific rates did not change in men. CONCLUSIONS: Heart failure hospitalizations have continued to increase from 1990 to 1999. Although aging and growth of the US population contribute to this trend, the increases are substantially influenced by changes in hospitalization rates in women.

Age Distribution↗
PubMed2004

Patterns of beta-blocker utilization in patients with chronic heart failure: experience from a specialized outpatient heart failure clinic.

BACKGROUND: Beta-blockers have been shown incontrovertibly to improve morbidity and survival in patients with heart failure. However, there is limited information regarding their use in clinical practice settings, and reasonable utilization targets for quality improvement initiatives have not been established. METHOD: We identified 500 consecutive patients with chronic heart failure seen at a specialized outpatient heart failure clinic from March 2001 to May 2001, and retrospectively extracted clinical and drug information from an electronic medical record. RESULTS: In this cross-sectional analysis, the rate of beta-blocker utilization was 69%. Seventy-five percent of patients had at least tried a beta-blocker. Among those with beta-blockers initiated, 16% experienced side effects that led to drug discontinuation (9.1%) or down-titration (6.9%) that was similar across all NYHA classes. A lower utilization rate of beta-blockers was observed in patients of advanced age and those with diabetes mellitus, concomitant antiarrhythmic therapy, and preserved left ventricular ejection fraction (P <.05). Respiratory disease remained the most common reason for withholding beta-blocker therapy, especially with severe obstructive (rather than restrictive) physiology. CONCLUSION: It appears that about 70% of patients with chronic heart failure can be successfully treated with a beta-blocker in a specialized heart failure outpatient setting where physicians are committed to beta-blocker use in heart failure. It is possible that subgroups with lower utilization rates can be targeted for quality improvement initiatives.

Adrenergic beta-Antagonists↗
PubMed2005

Prognostic value of elevated circulating heart-type fatty acid binding protein in patients with congestive heart failure.

BACKGROUND: Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured and is a novel marker for the diagnosis of acute myocardial infarction. The purpose of the present study was to examine the clinical significance of increased serum H-FABP levels in patients with congestive heart failure. METHODS AND RESULTS: Serum levels of H-FABP were measured in 179 patients admitted with congestive heart failure and 20 age-matched normal controls by using a sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a mean follow-up period of 20 months with the end points of cardiac death and progressive heart failure requiring rehospitalization. Serum levels of H-FABP were higher in patients with congestive heart failure than in control subjects (5.7 +/- 4.8 ng/mL versus 2.7 +/- 0.8 ng/mL, P < .01) and increased with advancing NYHA class (P < .01). The cardiac event rate was markedly higher in patients with elevated H-FABP levels than in those with normal levels (43% versus 7%, P < .0001). Furthermore, the Cox multivariate proportional hazard analysis revealed that the elevated H-FABP level was the only independent predictor for cardiac events (chi2= 7.397, P < .01). CONCLUSIONS: Elevation of H-FABP indicates latent and ongoing cardiomyocyte damage and identifies patients at high risk for future cardiac events in congestive heart failure.

Aged↗
PubMed2004

Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease.

OBJECTIVE: Ischemic heart disease accounts for 50% of all cardiovascular deaths and is the leading cause of congestive heart failure. Medical therapy, cardiac assist devices and surgical procedures including heart transplantation have limited efficiency and availability. Stem cell transplantation represents a new therapeutic opportunity for such patients. METHOD: Six patients with the diagnosis of ischemic cardiomyopathy were included in this study. All of the patients had clinical, radiological and echocardiographic signs of heart failure, and reduced left ventricular ejection fraction (LVEF< or =25%). They underwent coronary angiography and stress tests with dobutamine echocardiography, thallium scintigraphy and positron emission tomography to assess myocardial ischemia and viability. Peripheral stem cells were mobilized and collected by apheresis. They were transplanted into areas of injury with open-heart surgery. To increase blood flow to the engrafted areas, coronary artery by-pass surgery was also performed. RESULTS: The patients were followed at least for 4 months. Echocardiography, thallium scintigraphy and positron emission tomography were repeated after at least 6 weeks following surgery. There was a significant increase in life quality and NYHA class. Some benefit was documented on echocardiography, thallium scintigraphy, and positron emission tomography. CONCLUSION: This approach opens a new window in the treatment of 'no hope' patients with congestive heart failure.

Adult↗
PubMed2006

Disease management programs for heart failure: not just for the 'sick' heart failure population.

The development of disease management programs has been a major advance in heart failure care, bringing about significant improvements for the heart failure population, with reduction in readmission, better use of guideline therapy and improved survival. However, at present, the majority of such programs focus their attention only on the sicker segment of this population, with little application of this important service to the broader heart failure population, where potentially benefits may be even more impressive. This has led to an imbalance in the care of patients with heart failure, where aspects of management such as regular structured review and education are preferentially given to the group at the later stages of the natural history of the syndrome. This paper argues for a far wider application of the disease management program concept in heart failure care so as to bring the benefits of specialist care, patient education and follow-up to patients at an earlier stage in the natural history of heart failure.

Diffusion of Innovation↗
PubMed2005

Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database.

UNLABELLED: Approximately 50% of patients hospitalized for heart failure have preserved systolic function. These patients are more likely to be older, women, and hypertensive. Their duration of hospitalization is similar to that of heart failure patients with systolic dysfunction, but their in-hospital mortality risk is lower. This mortality risk is increased in the setting of renal insufficiency, and the two most important risk predictors are elevated blood urea nitrogen and systolic blood pressure < or = 125 mm Hg. Medical treatment strategies for patients with preserved systolic function are inconsistent and reflect the need for efficacious evidence-based treatment regimens. OBJECTIVES: The aims of this analysis were to describe the clinical characteristics, management, and outcomes of patients hospitalized for acute decompensated heart failure (HF) with preserved systolic function (PSF). BACKGROUND: Clinically meaningful characteristics of these patients have not been fully studied in a large database. METHODS: Data from >100,000 hospitalizations from the Acute Decompensated Heart Failure National Registry (ADHERE) database were analyzed. RESULTS: Heart failure with PSF was present in 50.4% of patients with in-hospital assessment of left ventricular function. When compared with patients with systolic dysfunction, patients with PSF were more likely to be older, women, and hypertensive and less likely to have had a prior myocardial infarction or be receiving an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. In-hospital mortality was lower in patients with PSF compared with patients with systolic dysfunction (2.8% vs. 3.9%; adjusted odds ratio [OR]: 0.86; p = 0.005), but duration of intensive care unit stay and total hospital length of stay were similar. Serum creatinine >2 mg/dl was associated with increased in-hospital mortality in both systolic function groups (PSF: 4.8%; systolic dysfunction: 8.4%; p < 0.0001), and the most powerful predictors of in-hospital mortality in both groups were blood urea nitrogen >37 mg/dl (OR: 2.53; 95% confidence interval [CI]: 2.22 to 2.87) and systolic blood pressure < or =125 mm Hg (OR: 2.58; 95% CI: 2.33 to 2.86). CONCLUSIONS: Heart failure with PSF is common and is characterized by a unique patient profile. Event rates are worrisome and reflect a need for more effective management strategies.

Aged↗
PubMed2006

Keeping the heart empty and beating improves preservation of hypertrophied hearts for valve surgery.

OBJECTIVE: This study was designed to determine whether keeping the heart empty and beating improved myocardial fluid homeostasis and energy metabolism of hypertrophied pig hearts in comparison with cardioplegic arrest. METHODS: Twenty piglets underwent a 8-weeks (corrected) ascending aortic banding to induce left ventricular hypertrophy. Isolated hypertrophied hearts were divided into 4 groups (n = 5 in each group). Two groups underwent normothermic normokalemic simultaneous perfusion. The other 2 groups were subjected to normothermic hyperkalemic simultaneous perfusion and used as controls. Intramyocardial hydrostatic pressure was monitored with a microtip pressure transducer. Volumes of intracellular and extracellular compartments and myocardial energy metabolism were monitored by using phosphorus 31 magnetic resonance spectroscopy. RESULTS: Normothermic normokalemic simultaneous perfusion (NNSP) maintained intramyocardial hydrostatic pressure at a significantly lower level (13.0 +/- 0.6 mm Hg) compared with normothermic hyperkalemic simultaneous perfusion (NHSP) (23.3 +/- 1.2 mm Hg) during a 90-minute preservation. NNSP maintained the normal volume of the intracellular compartment throughout the preservation period, whereas NHSP caused significant enlargement (to 123% +/- 6% of its normal volume) of the intracellular compartment. Expansion of the extracellular compartment during preservation was significantly less in the NNSP group (124% +/- 6%) than in the NHSP group (152% +/- 7%). NNSP maintained normal levels of phosphocreatine and adenosine triphosphate until coronary perfusion flow was reduced to 50% of the initial control level. No decrease in energy metabolites was observed in the NHSP group even when coronary perfusion flow was reduced to 10% of the initial control level. CONCLUSIONS: Keeping the heart empty and beating improves myocardial fluid homeostasis for hypertrophied hearts relative to cardioplegic arrest. Its ability to maintain energy metabolism depends on the degree of coronary stenosis. This technique may be a promising protective strategy for hypertrophied hearts.

Animals↗
PubMed2006

Ventricular fibrillation waveform characteristics are different in ischemic heart failure compared with structurally normal hearts.

BACKGROUND: For prolonged VF, perfusion of the myocardium by pre-shock chest compressions can improve myocardial readiness for successful defibrillation. Characteristics of the VF waveform correlate with the duration of VF when there is no structural heart disease. A "smart" automated external defibrillator (AED) could therefore analyze the VF waveform, determine if VF has been prolonged, and then direct rescuers to either deliver a shock first or chest compressions first. We hypothesized that ischemic heart failure might alter the waveform content of ventricular fibrillation compared with normal hearts, complicating the determination of VF duration. METHODS: Myocardial infarction was induced by ligating the proximal left coronary artery. Six weeks later, VF was then induced in 10 rats with myocardial infarction and heart failure (MI-CHF) and 9 control rats. Waveforms were analyzed for total signal amplitude, median frequency, dominant frequency and bandwidth (the frequency interval containing 50% of the total amplitude about the median frequency). RESULTS: All of these VF waveform characteristics were altered substantially in MI-CHF rats compared to normal controls. In particular, MI-CHF rats had decreased signal amplitude early in VF (p=0.02), a broader bandwidth (p=0.001) and different frequency characteristics over time (p<0.001). CONCLUSIONS: VF waveforms vary over time in a typical manner among rats with and without ischemic heart failure. However, the time-course and waveform characteristics of ventricular fibrillation are altered in rats with myocardial infarctions and ischemic heart failure compared to normal controls. These findings have important implications regarding the use of waveform analyses to determine the duration of VF.

Animals↗
PubMed1997

An epidemiologic perspective of systemic hypertension, ischemic heart disease, and heart failure.

Improvements in the identification and control of hypertension have helped define populations at risk for hypertension and delineated the role of hypertension as a risk factor in ischemic heart disease and heart failure. Epidemiologic data document the high prevalence of hypertension among the elderly and black populations. Beginning in the 1970s, a new perspective on the identification and treatment of hypertension began to emerge with greater emphasis on blood pressure control, particularly among these high-risk groups. By the early 1990s, most hypertensive individuals were being treated and blood pressure was under control in 55% of hypertensive persons overall. Although the importance of elevated diastolic pressure has traditionally been emphasized, in recent years the clinical implications of isolated systolic hypertension and the benefit of treating elevated systolic pressure have been recognized. Coronary heart disease is associated with definite hypertension (> or =160/95); however, the presence of other risk factors such as elevated plasma levels of cholesterol and high-density lipoprotein cholesterol, cigarette smoking, and diabetes mellitus create a synergy with even mild hypertension (140-159/90-94 mm Hg) to increase coronary risk. A different situation is present for cardiac failure. Data from the Framingham Heart Study demonstrate that hypertension, myocardial infarction, angina pectoris, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease were associated with an increased relative risk for cardiac failure. The relative risk for cardiac failure was greatest for persons with a previous myocardial infarction, and hypertension and previously diagnosed coronary heart disease were important precursors of cardiac failure.

Female↗
PubMed2000

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system.

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.

Analysis of Variance↗
PubMed2003

Natural killer cell and proinflammatory cytokine responses to mental stress: associations with heart rate and heart rate variability.

Associations between natural killer (NK) cell, proinflammatory cytokine stress responsivity, and cardiac autonomic responses (indexed by heart rate and heart rate variability) were assessed in 211 middle-aged men and women. Blood was drawn at baseline, immediately following color-word interference and mirror tracing tasks for the assessment of NK cell numbers, and 45 min post-stress for assessing plasma interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) responses. Heart rate variability was measured as the root mean square of successive differences (RMSSD) in R-R intervals. Increases in NK cell counts following stress were positively associated with heart rate responses independently of age, sex, socioeconomic status, smoking, and change in hematocrit. Heart rate 45 min post-stress was positively associated with plasma IL-6 post-stress, and with TNFalpha changes from baseline, independently of covariates. No relationship between immune responses and heart rate variability was observed. We conclude that individual differences in sympathetically-driven cardiac stress responses are associated with NK and proinflammatory cytokine responses to psychological stress.

Adult↗
PubMed1999

Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure.

OBJECTIVES: The purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms. BACKGROUND: Carvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure. METHODS: We retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients. RESULTS: Nonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function. CONCLUSIONS: Patients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.

Actuarial Analysis↗
PubMed2002

Effects of alcohol restriction on ambulatory blood pressure, heart rate, and heart rate variability in Japanese men.

We investigated the effects of alcohol restriction on ambulatory blood pressure (BP), heart rate, and heart rate variability in 33 Japanese male volunteers (37 +/- 1 years, mean +/- SE), who were all habitual drinkers. Subjects were told either to keep their usual drinking habits for 3 weeks (usual alcohol period), or to reduce alcohol intake by at least half of their usual drinking amount (reduced alcohol period). The ambulatory BP, heart rate, and electrocardiographic R-R intervals were measured during a 24-h period with a portable recorder on the last day of each period. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. The percentage of differences between adjacent normal R-R intervals >50 msec (pNN50) was also calculated. The amount of ethanol intake was significantly reduced from 70 +/- 5 mL/day in the usual alcohol period to 19 +/- 3 mL/day in the reduced alcohol period (P < .0001). The daytime systolic BP was significantly lower in the reduced alcohol period than in the usual alcohol period by 4 +/- 1 mm Hg (P < .05). The daytime and nighttime heart rate was significantly lower in the reduced alcohol period than in the usual alcohol (P < .001 for each). The pNN50 and the HF component were significantly higher in the reduced alcohol period than in the usual alcohol period (P < .0001 for each). The LF/HF ratio was significantly lower in the reduced period than in the usual period (P < .01). These results demonstrate that 3-week alcohol restriction produced reductions in ambulatory systolic BP, heart rate, and the index of sympathovagal balance, and augmentations of parasympathetic indices of heart rate variability in Japanese male drinkers.

Adult↗
PubMed2001

Convergence of distinct pathways to heart patterning revealed by the small molecule concentramide and the mutation heart-and-soul.

BACKGROUND: One of the earliest steps in heart formation is the generation of two chambers, as cardiogenic cells deployed in the epithelial sheet of mesoderm converge to form the nascent heart tube. What guides this transformation to organotypic form is not known. RESULTS: We have identified a small molecule, concentramide, and a genetic mutation called heart-and-soul (has) that disrupt heart patterning. Both cause the ventricle to form within the atrium. Here, we show that the has gene encodes PKC lambda. The effect of the has mutation is to disrupt epithelial cell-cell interactions in a broad range of tissues. Concentramide does not disrupt epithelial interactions, but rather shifts the converging heart field rostrally. What is shared between the concentramide and has effects is a reversal of the order of fusion of the anterior and posterior ends of the heart field. CONCLUSIONS: The polarity of cardiac tube assembly is a critical determinant of chamber orientation and is controlled by at least two distinct molecular pathways. Combined chemical/genetic dissection can identify nodal points in development, of special importance in understanding the complex patterning events of organogenesis.

Acrylamides↗