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Cardiac function after intermittent antegrade warm blood cardioplegia: contribution of the double-indicator dilution technique.

OBJECTIVE: To evaluate cardiac performance following coronary artery surgery using two different techniques of cardioplegia. DESIGN: Randomized prospective study. SETTING: Adult cardiothoracic intensive care unit in a university hospital. STUDY POPULATION: Thirty patients undergoing isolated coronary surgery. INTERVENTIONS: Patients were randomized to receive either intermittent antegrade warm blood cardioplegia with normothermic bypass (group 1) or combined antegrade and retrograde cold crystalloid cardioplegia with hypothermic bypass (group 2). Hemodynamic evaluation included conventional measurements from a pulmonary artery catheter and data obtained by thermal dye dilution utilizing an arterial thermistor-tipped fiberoptic catheter. RESULTS: The only major difference between groups was a significantly higher right atrial pressure in group 2, from 4 h to 24 h after surgery (8.8 +/- 2.6 vs. 11.8 +/- 3.2 mmHg at 4 h and 11 +/- 3.1 vs. 8.5 +/- 1.8 mmHg at 24 h, P = 0.04). After cold cardioplegia a significant increase in right atrial pressure was observed (7.5 +/- 3.1 before surgery vs. 11.4 +/- 3 mmHg at 8 h, P = 0.003) whereas right ventricular end diastolic volume index did not increase significantly, suggesting impaired right ventricular diastolic compliance in this group. CONCLUSIONS: Until 24 h after surgery cold cardioplegia is associated with impaired right ventricular filling, which seems better preserved by intermittent antegrade warm blood cardioplegia. End-diastolic volume measurement with the double-indicator technique allows differentiation between systolic and diastolic dysfunction.

Analysis of Variance↗

Doppler-derived parameters of diastolic left ventricular function in preterm infants with a birth weight <1500 g: reference values and differences to term infants.

Transmitral flow parameters in preterm and term infants were compared in order to study differences in signal expression and temporal dynamics of left ventricular diastolic function. In 63 preterm infants between 26 and 33 weeks of gestation and 102 term infants, a Doppler survey was performed during 6 months after birth. Early and atrial filling-time velocity integrals and peak velocities were significantly lower in the preterm neonates. Atrial filling parameters reached the level observed in term infants by 2 months of age. Peak early filling velocity was still lower for 2-month-old preterms and attained the term infants' level by 3 months of age. Preterm infants continued having high atrial filling fraction (AFF) (0.51+/-0.07) during 2 months after birth, while in term infants the fraction decreased continuously from 0.41+/-0.06 to 0.37+/-0.05. Isovolumic relaxation time (IVRT) was the only parameter without differences between preterm and term infants, and it decreased from 54+/-7 ms in neonates to 41+/-4 ms over 3 months. Stroke volume passing the mitral valve doubled in preterm (4+/-1 to 7.9+/-1.5 ml/cm2), but increased by only 37% (6.9+/-1.6 to 9.5+/-2.2 ml/cm2) in term infants. Our observations show that the maturational period of diastolic function appears prolonged in preterm infants. As preterm infants have to cope with a higher physiologic preload augmentation during growth, part of the delay in parameter changes might be caused by preload stress rather than by persistence of functional impairment. Although doing well under physiological conditions, preterm neonates may be at higher risk for diastolic dysfunction than term infants when an additional preload challenge is encountered.

Diastole↗

The influence of diastolic and systolic function on exercise performance in heart failure due to dilated cardiomyopathy or ischemic heart disease.

BACKGROUND: Peripheral adaptations and ventricular abnormalities influence physical performance in chronic heart failure. However, the role of the heart in determining exercise capacity has not been completely elucidated. AIMS: To define cardiac determinants of exercise capacity in patients with dilated cardiomyopathy. METHODS: In 101 patients with heart failure (NYHA class II-III) due to primary or ischemic dilated cardiomyopathy we measured peak exercise oxygen consumption (Pvo2), left ventricular ejection fraction (EF), left and right atrial and ventricular cavity dimensions, mitral and tricuspid flows. Patients were subdivided in class A (Pvo2 > 20 ml/min per kg; n = 44), class B (Pvo2 16-20 ml/min per kg; n = 42) and class C (Pvo2 < 16 ml/min per kg; n = 15). RESULTS: Left ventricular diastolic and systolic dimensions, left atrial diameter, right atrial and ventricular areas were greater in class C than in class B and A; EF was lower in class C than in the other two classes; mitral peak flow velocity at early diastole (PFVE) and the ratio between early and late peak flow velocity (PFVE/PFVA) were higher in class C; mitral and tricuspid deceleration time (DT) in class B and A significantly exceeded those in class C. Peak vo2 was correlated with left and right ventricular dimensions, left atrial diameter, EF, mitral PFVE and PFVE/PFVA, mitral and tricuspid DT. Left ventricular EF, DT of the mitral valve and left ventricular diastolic diameter were independent predictors of peak vo2 at multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy Pvo2 is related to left and right ventricular dimensions, left and right ventricular filling pattern and EF. Both systolic and diastolic dysfunction influence functional capacity.

Blood Flow Velocity↗

Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis.

BACKGROUND: MR tissue tagging allows the noninvasive assessment of the locally and temporally resolved motion pattern of the left ventricle. Alterations in cardiac torsion and diastolic relaxation of the left ventricle were studied in patients with aortic stenosis and were compared with those of healthy control subjects and championship rowers with physiological volume-overload hypertrophy. METHODS AND RESULTS: Twelve aortic stenosis patients, 11 healthy control subjects with normal left ventricular function, and 11 world-championship rowers were investigated for systolic and diastolic heart wall motion on a basal and an apical level of the myocardium. Systolic torsion and untwisting during diastole were examined by use of a novel tagging technique (CSPAMM) that provides access to systolic and diastolic motion data. In the healthy heart, the left ventricle performs a systolic wringing motion, with a counterclockwise rotation at the apex and a clockwise rotation at the base. Apical untwisting precedes diastolic filling. In the athlete's heart, torsion and untwisting remain unchanged compared with those of the control subjects. In aortic stenosis patients, torsion is significantly increased and diastolic apical untwisting is prolonged compared with those of control subjects or athletes. CONCLUSIONS: Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

Adult↗

Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation.

BACKGROUND: The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau. METHODS AND RESULTS: Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg. CONCLUSIONS: This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.

Animals↗

Left ventricular hypertrophy, compliance and ventricular filling.

A total of 20 untreated hypertensive patients were divided into two equal groups matched for sex, age and blood pressure but with [mean diastolic wall thickness (MDWT) greater than 1.2 cm] or without (MDWT greater than 1.2 cm) left ventricular hypertrophy (LVH). All patients underwent pulsed doppler echocardiography and 99Tc radionuclide ventriculography at rest to assess diastolic and systolic abnormalities. In hypertensives with LVH the interventricular wall thickness, posterior wall thickness and relative diastolic wall thickness were significantly (P less than 0.01) higher and peak filling rate was significantly (P less than 0.01) lower than in hypertensives without LVH. The indices of systolic function, however, were not significantly different in the two patient groups. In hypertensives without LVH peak filling rate directly correlated with heart rate, whereas in those with LVH peak filling rate directly correlated with heart rate and the ratio of peak velocity of early left ventricular filling : peak velocity of late left ventricular filling due to atrial contraction. It is concluded that diastolic parameters may be useful tools for assessing myocardial compliance and may be effective markers of diastolic dysfunction.

Adult↗

Elevated B-type natriuretic peptide levels after anthracycline administration.

BACKGROUND: Cardiotoxicity leading to congestive heart failure is a complication of the anthracyclines. Biochemical methods to diagnose and monitor cardiac function after anthracycline administration would be most useful. We examined the diagnostic role of B-type natriuretic peptide (BNP), a potent biochemical marker of left ventricular dysfunction, in patients administered anthracyclines. METHODS: Twenty-seven consecutive patients receiving anthracyclines were investigated by serial measurements of BNP levels and other cardiac neurohormones (A-type natriuretic peptide, renin, aldosterone, angiotensin II, norepinephrine, and epinephrine) and myocardial markers (creatine kinase-MB and myosin light chain). Echocardiography was done to assess systolic (ejection fraction) and diastolic (mitral inflow A/E ratio) functions. RESULTS: Of the examined cardiac biochemical markers, BNP levels alone showed marked elevations to abnormal levels after anthracycline administration. Most patients showed transient increases (peak at 3 to 7 days). Patients with persistent elevations showed a poor prognosis. A/E ratio also correlated with increases in BNP levels in selected patients, which may suggest that raised BNP levels are reflective of induced diastolic dysfunction. CONCLUSIONS: Our studies suggest the possible use of BNP levels to assess the cardiac state after anthracycline administration. BNP levels most likely reflect cardiac tolerance to the cardiotoxic agent. Serial BNP profiles also suggest persistent elevations to be associated with potentially decompensatory states in contrast to tolerable transient increases. Diagnosis of degree of cardiac tolerance by response to drug administration may be analogous to use of stress testing (exercise) to help define underlying left ventricular dysfunction.

Adult↗

Left ventricular diastolic function in hypertension: a 4 year follow-up study.

In order to assess the long term effects of antihypertensive treatment on left ventricular diastolic function, 26 hypertensive patients were followed up for a mean of 4.25 years with two-dimensional and Doppler echocardiography. A significant reduction in left ventricular mass index was first apparent after 9 months of therapy (mean (S.D.) 124 (22) vs. 114 (18) g/m2, P < 0.01), and this was maintained over the 4.25 year period (124 (22) vs. 117 (17) g/m2, p < 0.05). At 9 months there was no change in either isovolumic relaxation time (108 (26) vs. 108 (17) ms, P = N.S.) or left ventricular filling as assessed by peak flow velocity E/A ratio (0.94 (0.22) vs. 0.95 (0.27), P = N.S.). However, after 4.25 years there was a significant improvement in IVRT (108 (26) vs. 83 (11) ms, P < 0.01) with a trend towards an improved peak flow velocity E/A ratio, although this did not reach statistical significance (0.95 (0.27) vs. 1.02 (0.26), P = N.S.). Of the 14 patients who had an abnormal isovolumic relaxation time at baseline, 12 normalised and 2 improved. These findings suggest that left ventricular diastolic dysfunction in hypertension may be reversed by prolonged antihypertensive treatment.

Adult↗

Detection of heart transplant rejection in adults by echocardiographic diastolic indices: a systematic review of the literature.

BACKGROUND: Diastolic dysfunction is often used as a marker of allograft rejection in patients with cardiac transplantation. However, the strength of evidence to support this approach needs to be determined. METHODS: We sought to review and evaluate the quality of the published data about the use of diastolic indices (DI) to predict a rejection episode. A MEDLINE search was performed to identify English-language articles published from 1967 to 2005 that used DI to predict rejection episodes. The references of each retrieved article were scanned to identify additional relevant articles. Studies showing the correlation between echocardiography findings and biopsy results were included. Articles were abstracted using a standardized instrument designed by the authors. Quality was assessed using standardized criteria. Discrepancies were adjudicated by consensus. RESULTS: Nineteen studies met the inclusion criteria. Quality of studies varied widely. Thirteen studies explicitly stated having an independent blind comparison with a reference standard, 4 studies presented reproducibility information, no studies presented likelihood ratios, and only 11 of them provided sensitivity and specificity. Left ventricular diastolic indices evaluated included inflow Doppler early diastolic (E) wave pressure half-time (sensitivity 23%-87%, specificity 76%-98%) and isovolumetric relaxation time (sensitivity 28%-85%, specificity 80%-98%), as well as tissue Doppler early diastolic (E') wave (sensitivity 69%-76% and specificity 59%-88%) and late diastolic (A') wave (sensitivity 67%-82%, specificity 49%-53%). CONCLUSION: Because of inconsistent quality of the studies and low sensitivities, the current literature does not support the use of DI by echocardiography as a screening test in the prediction of allograft rejection in the heart transplantation population. Larger controlled studies incorporating newer DI such as tissue Doppler are needed.

Adult↗

Comparison of usefulness of echocardiographic Doppler variables to left ventricular end-diastolic pressure in predicting future heart failure events.

We sought to determine whether the echocardiographic Doppler parameters of left ventricular diastolic dysfunction predict future heart failure (HF) events and, if so, which parameters best predict HF. We also examined whether the predictive ability of echocardiographic Doppler parameters was related to their prediction of left ventricular end-diastolic pressure (LVEDP). We studied patients who underwent cardiac catheterization and echocardiography performed within a 30-day period. The end point was HF, defined as new-onset or recurrent HF diagnosed by a physician and requiring the initiation or modification of treatment of HF. We identified 289 patients (mean age 63.5 +/- 12.6 years) with a mean follow-up of 10.9 +/- 10.2 months. A total of 24 HF events occurred. LVEDP was a significant predictor of HF univariately and independently in multiple regression models after adjustment for ejection fraction. In Cox models adjusted for age, gender, LVEDP, and ejection fraction, only the left atrial volume index and early mitral inflow to early diastolic tissue velocity (E/e') ratio remained predictive of HF. A multiple regression model, including all echocardiographic variables, showed a persistent, although attenuated, relation of early to late mitral inflow velocity (E/A) ratio and E/e' with LVEDP (p = 0.06 and p = 0.002, respectively). The addition of E/e' or the left atrial volume indexed to body surface area, but not E/A, to the clinical history and left ventricular ejection fraction provided incremental prognostic information. A LVEDP of > or =20 mm Hg, E/e' ratio of > or =15, and left atrial volume index of > or =23 ml/m(2) identified those with a higher risk of HF. In conclusion, invasively determined LVEDP is an independent predictor of future HF events. E/e' and the left atrial volume indexed to body surface area are the best independent predictors of future HF and provide prognostic information incremental to the clinical history and left ventricular ejection fraction.

Adult↗

Diabetic cardiomyopathy.

Prior to 1972, the increased cardiovascular morbidity and mortality that diabetics endure had been attributed to vascular disease. In 1972, Rubler et al. proposed the existence of a diabetic cardiomyopathy based on their expereince with four adult diabetic patients who suffered from congestive heart failure (CHF) in the absence of discernable coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. Alternative explanations for CHF, such as anemia and vascular and renal disease in these four patients, gave rise to criticisms, but a wave of subsequent studies in the 1970s and 1980s provided credence to this new disease entity. This review of the studies done since 1972 appears to support the concept of a diabetic cardiomyopathy independent of atherosclerotic cardiovascular disease. The exact mechanism is still questionable, and several mechanisms have been proposed including small and microvascular disease, autonomic dysfunction, metabolic derangements, and interstitial fibrosis. However, the weight of evidence leans toward the development of fibrosis, possibly caused by the accumulation of a peroxidase acid schiff (PAS)-positive glycoprotein, leading to myocardial hypertrophy and diastolic dysfunction.

Cardiomyopathy, Dilated↗

Noninvasive assessment of systolic and diastolic left ventricular function in patients with chronic severe anemia: a combined M-mode, two-dimensional, and Doppler echocardiographic study.

Thirty-one patients with chronic severe anemia of more than 3 months' duration (hemoglobin less than 7 gm/dl) and no underlying heart disease were studied by means of M-mode, two-dimensional, and Doppler echocardiography; an equal number of normal control subjects was also studied. There are conflicting reports regarding the influence of chronic severe anemia on systolic myocardial function, but diastolic function has not been systematically assessed. It is also uncertain whether anemia alone can cause heart failure in a structurally normal heart. We therefore performed a detailed study of echocardiographic indexes of systolic and diastolic left ventricular function in these patients. We found that patients with anemia have significantly faster heart rates and lower diastolic and mean blood pressures than normal subjects. They also have a significantly elevated cardiac output and stroke volume and larger left ventricles. Left ventricular contractility, assessed by the end-systolic stress-dimension relationship, was enhanced. There was no systematic evidence of diastolic dysfunction by Doppler assessment of mitral inflow. There was also no clinical evidence of congestive heart failure. We conclude that chronic severe anemia leads to a hyperdynamic state with systolic hyperfunction and no impairment of diastolic function. Anemia does not lead to congestive heart failure in the absence of underlying heart disease.

Adult↗

Regression of left ventricular hypertrophy and improvement of diastolic function in hypertensive patients treated with telmisartan.

OBJECTIVES: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. METHODS: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mmHg, diastolic blood pressure [DBP] >90 mmHg) and mild-to-moderate LV hypertrophy (LV mass index related to body surface area [LVMI] 117-150 g/m2 for men and 105-150 g/m2 for women) treated with telmisartan monotherapy 40-80 mg once daily for 1 year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood pressure was also monitored at all visits. Diastolic function was assessed by examination of transmitral inflow and pulmonary vein flow patterns. RESULTS: Telmisartan reduced blood pressure; after 12 months, the mean+/-S.D. SBP and DBP were reduced from 144+/-10 to 126+/-8 mmHg (p<0.001) and from 98+/-8 to 86+/-7 mmHg (p<0.001), respectively. The LVMI was decreased from 119+/-7 to 109+/-3 g/m2 (p<0.001) after 12 months' telmisartan treatment. All patients had diastolic dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern of transmitral inflow was present in 21% of patients. The regression of LV hypertrophy observed after 12 months was associated with increased peak early diastolic velocity/peak late diastolic velocity ratio from 0.60+/-0.18 to 0.83+/-0.20 (p<0.001), shortened isovolumic relaxation time (IVRT) from 110+/-13 to 105+/-13 ms (p<0.001), and decreased deceleration time from 229+/-30 to 215+/-28 ms (p=0.002). Univariate analysis showed that shortened IVRT was related to a reduction in the LVMI and LA maximal and minimal volumes. In the multivariate analysis, the reduction in LVMI and the reduction in LA maximal and minimal volumes were independently associated with IVRT reduction. CONCLUSIONS: Telmisartan 40-80 mg is effective in LV hypertrophy regression in hypertensive patients. The reduction in LVMI due to telmisartan monotherapy was associated with a significant improvement of diastolic filling parameters and with a significant reduction of LA volumes.

Benzimidazoles↗

Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo.

Abnormal relaxation of the heart, termed diastolic dysfunction, is a significant and growing problem that is a major cause of heart failure in the aged population. The potential of gene transfer of parvalbumin (Parv), a cytoplasmic calcium-binding protein, to improve diastolic function in the aged myocardium in vivo was evaluated. Despite evidence for an early developmental influence on the efficiency of Ad5 striated muscle transduction, results show that Ad5 gene transfer efficiency to adult cardiac myocytes in vitro is identical in young and old rats, suggesting that the basic processes of adenovirus binding and internalization are unaffected by aging. In contrast, Ad5-mediated Parv gene transfer to the myocardium in vivo is reduced in old rats compared to young rats. Nonetheless, Parv gene transfer and expression in vivo were sufficient to improve tau, a load-independent indicator of diastolic function, assessed using catheter-based micromanometry in the aged myocardium. These results suggest that expression of the calcium buffer Parv may represent an effective approach to functional correction of the failing heart in the aging.

Adenoviridae↗

Duration of pulmonary venous atrial reversal flow velocity and mitral inflow a wave: new measure of severity of cardiac amyloidosis.

Transmitral Doppler flow patterns of patients with cardiac amyloidosis evolve from an early impaired relaxation to an advanced restrictive pattern. This reflects increasing severity of diastolic dysfunction and hence left ventricular filling pressures. The duration of the pulmonary venous atrial reversal flow was recently shown to exceed that of the mitral inflow A wave in patients with left ventricular end-diastolic pressure greater than 15 mm Hg. The objective of this study was to assess the utility of this index as a measure of the severity of cardiac amyloidosis. Comprehensive transthoracic 2-dimensional and pulsed-wave Doppler echocardiograms of the pulmonary venous and transmitral flows were made of 23 patients (10 women) with biopsy-proven diagnosis of primary systemic amyloidosis and of 49 subjects as age-matched normal controls. The amyloidosis group was divided into non-restrictive and restrictive subgroups on the basis of the patients' transmitral inflow deceleration time (>150 and < or =150 ms, respectively). The durations of the pulmonary venous atrial reversal and mitral inflow A wave were measured, and the differences between the flow durations were compared with the control and published data in the nonrestrictive and restrictive groups. The mean duration of the pulmonary venous atrial reversal was significantly longer in the amyloid than the control group (P < .01). The mean duration of the mitral inflow A wave was significantly shorter in the restrictive group than both the nonrestrictive and the control groups (P < .05). The duration of the pulmonary venous atrial reversal exceeded that of the mitral inflow A wave in all patients with cardiac amyloidosis. The difference in duration between pulmonary venous atrial reversal and mitral inflow A wave was significantly greater in the amyloidosis group compared with the normal group, and this index varied significantly within the amyloid group between the abnormal relaxation and the restrictive groups. The difference in the duration between the pulmonary venous atrial reversal and the mitral inflow A wave is a reliable index of diastolic function and can be used to assess the severity of cardiac amyloidosis.

Adult↗

Bisoprolol improves echocardiographic parameters of left ventricular diastolic function in patients with systemic hypertension.

Left ventricular (LV) diastolic dysfunction (LVD) is a common complication secondary to hypertension. It has been reported that bisoprolol is effective in reducing blood pressure and has beneficial cardiac effects in patients with hypertension. However, its effect on LV diastolic function has not been studied in detail. In this study, we sought to determine bisoprolol's effect on left ventricle diastolic function. Data from 25 patients were statistically analyzed. Peaks E and A wave, E/A ratio, isovolumetric relaxation time and E wave deceleration time were measured echocardiographically. Doppler echocardiography measurements after bisoprolol treatment revealed an improvement in LV diastolic function. In conclusion, our results show that treatment with bisoprolol, improves echocardiographic parameters of LV diastolic function after 3 months of treatment.

Antihypertensive Agents↗

Amrinone increases ventricular contractility and diastolic compliance in endotoxemia.

Systolic and diastolic dysfunction occur during human septic shock, and sensitivity to beta-adrenergic agents is reduced. We sought to determine whether amrinone, an inotropic agent independent of beta-receptors, increases left-ventricular contractility or diastolic compliance after endotoxin infusion. We measured left-ventricular volume (using a conductance catheter) and pressure (using a Millar catheter) before and after administering amrinone (4.5 mg/kg i.v., then 10 micrograms/kg/min) to six endotoxemic and seven control pigs. The slope of the end-systolic pressure-volume relationship, Ees, was used as the primary measure of contractility. Diastolic stiffness was characterized using stiffness parameters taken from pressure-volume relationships (k) and from pressure-volume strain relationships. Amrinone increased Ees from a median of 10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 to 18.6) (p < 0.05) in the endotoxin group (p < 0.05). Amrinone decreased diastolic stiffness (k) in the endotoxin group by 35 +/- 18% (p < 0.05). Amrinone did not significantly change Ees or k in the control group. Mean arterial pressure decreased after endotoxin infusion from 117 +/- 23 mm Hg to 76.5 +/- 14.9 mm Hg (p < 0.05), and decreased further after amrinone to 62.0 +/- 14.8 mm Hg (p < 0.05). We conclude that in this model of sepsis, amrinone may beneficially increase systolic contractility and diastolic compliance, but may dangerously decrease an already low mean arterial pressure.

Amrinone↗

Does treating subclinical hypothyroidism improve markers of cardiovascular risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.

Cardiovascular Diseases↗