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PubMed2006

The utility of pulsed tissue Doppler parameters for the diagnosis of advanced left ventricular diastolic dysfunction.

OBJECTIVE: The evaluation of diagnostic value of pulsed tissue Doppler (TD) parameters (calculated from six points of mitral annulus and separately measured in the lateral part of mitral annulus) for the detection of pseudonormal mitral inflow pattern. METHODS AND RESULTS: Among 200 persons examined by transthoracic echocardiography group with E/A value between 1 and 2 was selected and divided to normal (54 subjects, early wave deceleration time, Edt > or = 150 msec) and pseudonormal (23 patients, Edt < 150 msec together with prolonged difference between duration of atrial reversal flow in pulmonary vein and mitral flow in atrial phase, delta Ar > or = 20 msec) inflow. Wide spectrum of TD parameters was compared between the selected groups. In normal inflow, average peak velocities of early and atrial phase of diastolic mitral annulus motion were significantly higher: 11.0 +/- 2.6 versus 8.9 +/- 3.5 cm/sec; (P = 0.005) and 12.0 +/- 2.2 versus 10.0 +/- 3.0 cm/sec; (P = 0.002), respectively. Ratio of peak early mitral wave velocity to peak velocity of annulus motion in early phase (Ev/E'v avr) was higher in the pseudonormal pattern: 9.8 +/- 3.7 versus 7.0 +/- 2.0, respectively (P < 0.001). For the value of Ev/E'v avr > 10.2, 70% accuracy for the diagnosis of pseudonormalization was detected. For the parameters measured in the lateral part of mitral annulus similar relationships in the early filling phase were detected but did not reach statistical significance in the atrial phase. CONCLUSIONS: Pulsed TD offers good accuracy for the diagnosis of pseudonormalization with increased ratio of peak early mitral wave velocity to peak velocity of mitral annulus being the optimal predictor of advanced diastolic dysfunction.

Blood Flow Velocity↗
PubMed1990

Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction.

This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mg.kg-1.day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increased, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

Animals↗
PubMed2004

Right ventricular diastolic dysfunction and patent foramen ovale causing profound cyanosis.

A 73 year old woman presented with profound central cyanosis and a history of a minor stroke. She had normal heart morphology, normal pulmonary artery pressure, and a normal coronary angiography. A patent foramen ovale (PFO) with a massive right to left shunt was demonstrated at the atrial level, with normal pulmonary venous saturations and PO2 values. This rare, age related case of right ventricular diastolic dysfunction in a normotensive patient revealed a generous PFO allowing a pronounced right to left shunt.

Aged↗
PubMed1995

Obesity and left ventricular diastolic dysfunction.

To assess the influence of obesity on left ventricular function, 20 obese women (mean body mass index (BMI) 33.8 +/- 3.1 kg/m2 and mean age 31.1 +/- 2.4 years) without evidence of heart disease were evaluated by echocardiography. Obese subjects had greater left ventricular mass index (103 +/- 22 g/m2, 76 +/- 18 g/m2; P < 0.0001) and augmented fractional shortening (39 +/- 2.6%, 36 +/- 0.1%; P < 0.0001) than normals. Isovolumic relaxation time was prolonged in the obese group (92 +/- 11 ms) as compared with the control group (76 +/- 11 ms; P < 0.0001). The ratio of peak early and atrial filling velocities was significantly lower (1.2 +/- 0.4, 1.9 +/- 0.6; P < 0.0001) and atrial contribution was higher (39 +/- 9, 25 +/- 5; P < 0.0001) in obese subjects than in normals. Shortened deceleration time was measured in obese subjects (142 +/- 30, 179 +/- 20 ms; P < 0.0001). In conclusion, obesity causes relaxation and early filling abnormalities and diastolic filling is compensated by augmented atrial contribution. Diastolic dysfunction is an early indicator of cardiac involvement in obesity.

Adult↗
PubMed1993

Left ventricular systolic and diastolic dysfunction in the acute phases of myocardial ischaemia and infarction, and in the later phases of recovery. Function follows morphology.

Myocardial ischaemia and infarction result in major changes in myocardial function, due to the metabolic and structural cause. The observed morphological changes may be macroscopic--as in clinical myocardial infarction, microscopic--as in severe, prolonged ischaemia, or ultramicroscopic--in regard to the collagen matrix. Recognition of the vulnerability of these structures to the metabolic and mechanical stresses associated with severe ischaemia or infarction allows an understanding of the processes of acute dilatation, late adverse remodelling and compensatory hypertrophy, which determine both systolic and diastolic dysfunction and define the principal clinical complications. Morphology--'Form'--is the primary determinant of function, while metabolic and other factors are secondary, variably dependent on the integrity of structure.

Animals↗
PubMed1988

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy.

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Parallel gene expressions of IL-6 and BNP during cardiac hypertrophy complicated with diastolic dysfunction in spontaneously hypertensive rats.

UNLABELLED: There is increasing evidence showing that inflammation is involved in heart failure. However, heart failure may differ greatly due to different aetiologies. The role of inflammation in hypertensive heart failure, particularly in the early stage of cardiac dysfunction, has not been studied completely. This study aims at finding out whether inflammation is involved in the early stage of heart dysfunction due to hypertension. METHODS: Ten spontaneously hypertensive rats (SHR) and ten age-matched Wistar rats were used. Cardiac morphology and function, as well as coronary flow reserve, were examined by echocardiography. mRNAs for cytokines and brain natriuretic peptide were determined by RT-PCR. RESULTS: The results demonstrate cardiac hypertrophy with increased heart/body weight ratio in SHR. Echocardiographic examination has shown that SHR developed diastolic heart dysfunction as determined by tissue Doppler without decrease in systolic function. In heart biopsies, there were increased mRNA levels for interleukin-6 and brain natriuretic peptide whereas decreased mRNA for interleukin-2, beta adrenergic receptor, interferon and NFkb in SHR as compared to WKY group. Coronary flow remained unchanged in both groups. CONCLUSION: SHR developed cardiac hypertrophy complicated with diastolic heart dysfunction with increased expression of brain natriuretic peptide, down-regulation of beta adrenergic receptors and simultaneous up-regulation of IL-6, which indicates active proinflammatory process as, at least partly, underlying mechanism during the early stage when cardiac hypertrophy associated with diastolic dysfunction occurs.

Animals↗
PubMed1995

Effects of lisinopril on congestive heart failure in normotensive patients with diastolic dysfunction but intact systolic function.

This study examined the effects of lisinopril on diastolic function in 12 normotensive patients (mean age 72 years) with symptomatic congestive heart failure, intact left ventricular systolic function and abnormal diastolic function secondary to ischaemic heart disease in a placebo-controlled double blind crossover study, with each treatment dosed orally for 5 continuous weeks. Compared to placebo, lisinopril significantly decreased blood pressure, increased plasma renin activity without altering heart rate or plasma norepinephrine. There was no statistically significant improvement with lisinopril in radionuclide derived peak filling rate and time to peak filling rate, in Doppler echocardiographic measurements of the ratio of peak flow velocity in early diastole to the peak flow velocity of atrial contraction (E:A ratio) and in visual analogue scales of symptoms. Thus, although angiotension converting enzyme inhibitors may have an established role in the treatment of heart failure secondary to left ventricular systolic dysfunction, its use in patients with isolated diastolic dysfunction remains unclear.

Aged↗
PubMed1990

Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure.

Intracellular Ca2+ release and reuptake are necessary for normal contraction and relaxation of the human heart. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited two distinct components. Muscles from the failing hearts showed a diminished capacity to restore a low resting Ca2+ level during diastole. These data obtained in actively contracting human myocardium suggest that intracellular Ca2+ handling is abnormal and might cause both systolic and diastolic dysfunction in heart failure. The inotropic effectiveness of drugs that act to increase intracellular levels of cyclic adenosine monophosphate (AMP), such as beta-adrenergic agonists and phosphodiesterase inhibitors, was markedly reduced in muscles from patients with heart failure. In contrast, the effectiveness of inotropic stimulation with drugs that act by cyclic AMP-independent mechanisms, such as the cardiotonic steroids and DPI 201-106, were preserved. Stimulation of intracellular cyclic AMP production by the adenylate cyclase activator forskolin restored the inotropic response to phosphodiesterase inhibitors. These studies indicate that an abnormality in cyclic AMP production may be a fundamental defect in patients with end-stage heart failure that may markedly diminish the effectiveness of agents that depend on generation of this nucleotide for a positive inotropic effect. Moreover, deficient production of cyclic AMP seems, at least in part, to account for the reversal of the force-frequency relation that characterizes failing myocardium. Of interest, direct measurement of total cellular cyclic AMP content and protein kinase activity did not reveal significant differences between the control and myopathic tissue, suggesting the presence in human ventricular muscle of physiologically distinct compartmentalized pools of cyclic AMP. Finally, changes in the sensitivity of the contractile apparatus to Ca2+ also seem to play an important role in the differential responsiveness to drugs of myopathic versus normal human myocardium.

Calcium↗
PubMed2003

Cardiac lipid accumulation associated with diastolic dysfunction in obese mice.

Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

Animals↗
PubMed2005

Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy.

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Atrial Natriuretic Factor↗
PubMed2005

Increased collagen deposition and diastolic dysfunction but preserved myocardial hypertrophy after pressure overload in mice lacking PKCepsilon.

Overexpression and activation of protein kinase C-epsilon (PKCepsilon) results in myocardial hypertrophy. However, these observations do not establish that PKCepsilon is required for the development of myocardial hypertrophy. Thus, we subjected PKCepsilon-knockout (KO) mice to a hypertrophic stimulus by transverse aortic constriction (TAC). KO mice show normal cardiac morphology and function. TAC caused similar cardiac hypertrophy in KO and wild-type (WT) mice. However, KO mice developed more interstitial fibrosis and showed enhanced expression of collagen Ialpha1 and collagen III after TAC associated with diastolic dysfunction, as assessed by tissue Doppler echocardiography (Ea/Aa after TAC: WT 2.1+/-0.3 versus KO 1.0+/-0.2; P<0.05). To explore underlying mechanisms, we analyzed the left ventricular (LV) expression pattern of additional PKC isoforms (ie, PKCalpha, PKCbeta, and PKCdelta). After TAC, expression and activation of PKCdelta protein was increased in KO LVs. Moreover, KO LVs displayed enhanced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), whereas p42/p44-MAPK activation was attenuated. Under stretch, cultured KO fibroblasts showed a 2-fold increased collagen Ialpha1 (col Ialpha1) expression, which was prevented by PKCdelta inhibitor rottlerin or by p38 MAPK inhibitor SB 203580. In conclusion, PKCepsilon is not required for the development of a pressure overload-induced myocardial hypertrophy. Lack of PKCepsilon results in upregulation of PKCdelta and promotes activation of p38 MAPK and JNK, which appears to compensate for cardiac hypertrophy, but in turn, is associated with increased collagen deposition and impaired diastolic function.

Animals↗
PubMed1991

Normalization of Doppler indices of diastolic dysfunction during pacing is a sign of ischemic mitral regurgitation.

Twenty-three patients with angina who were undergoing diagnostic cardiac catheterization underwent cardiac pacing with simultaneous hemodynamic and Doppler echocardiographic evaluation to assess the effects of pacing-induced ischemic on mitral valve velocity. Seventeen patients had significant coronary artery disease, and six patients had normal coronary arteries. Doppler and hemodynamic measurements were performed at rest and immediately after pacing was discontinued to 91% +/- 7% of maximal predicted heart rate. Seven patients experienced new or significant increases in severity of mitral regurgitation after pacing as revealed by Doppler examination. This group had a significant increase (p = 0.007) in early but not in late peak filling velocities immediately after pacing was discontinued, with a resultant decrease in late to early ratios, which decreased from 1.01% +/- 0.12 to 0.70% +/- 0.19 (p = 0.006). Left ventricular end-diastolic pressure increased significantly from 16.7% +/- 6.8 mm Hg to 29.4% +/- 5.3 mm Hg after cardiac pacing (p less than 0.001). Patients with coronary disease who did not develop mitral regurgitation also had significant increases in left ventricular end-diastolic pressure from 18.7% +/- 5.8 mm Hg to 24.3% +/- 8.6 mm Hg (p less than 0.05). There were no changes in late or early wave amplitude, late to early ratio, or other Doppler measurements in any of the other groups. We conclude that mitral regurgitation caused by pacing-induced myocardial ischemia normalizes Doppler indices of mitral inflow, which in turn, may mask persistent or worsened left ventricular diastolic dysfunction.

Adult↗
PubMed2004

Both systolic and diastolic dysfunction characterize nonischemic inhibition of myocardial energy metabolism: an experimental strain rate echocardiographic study.

BACKGROUND: Ischemia is primarily a metabolic event. However, regional functional changes can be affected by structural alterations. We developed an experimental model of sole myocardial energy metabolism inhibition and characterized the resulting regional dysfunction. METHODS: In 12 pigs, we regionally inhibited creatine kinase (CK) and, consequently, myocyte high-energy phosphate transfer by intracoronary administration of iodoacetamide. Myocardial biopsies for CK activity and structural analyses and strain rate (SR) echocardiography scans were obtained at baseline and 60 minutes after iodoacetamide administration. Plasma levels of the CK isoenzyme MB and troponin I were assessed to determine possible myocardial damage. RESULTS: CK activity in the iodoacetamide-perfused myocardium decreased to 0.5% of the original value and was accompanied by a reduction in peak systolic SR ( P < .0001), end-systolic strain ( P < .0001), and peak SRs of myocardial early and late filling waves ( P < .0001). Microscopy showed contracture without sarcomere disruption. Plasma levels of CK isoenzyme MB and troponin I did not change. CONCLUSIONS: Regional inhibition of myocyte energetics leads to both systolic and diastolic dysfunction by SR echocardiography, but the presence of a residual phosphotransfer protects microstructural integrity.

Animals↗
PubMed1995

Normalization of diastolic dysfunction in aortic stenosis late after valve replacement.

BACKGROUND: The remodeling of the left ventricle in patients with aortic stenosis after aortic valve replacement (AVR) is a complex process involving structural and functional changes. METHODS AND RESULTS: Twenty-two patients were included in the present analysis. Twelve patients with severe aortic stenosis were studied before surgery, early (22 +/- 8 months) and late (81 +/- 22 months) after AVR using left ventricular biplane angiograms, high-fidelity pressure measurements, and endomyocardial biopsies. Ten healthy subjects were used as controls. Left ventricular systolic function was assessed from biplane ejection fraction; and diastolic function from the time constant of relaxation, the peak filling rate, and the myocardial stiffness constant. Left ventricular structure was evaluated from interstitial fibrosis, fibrous content, and muscle fiber diameter. Left ventricular muscle mass was significantly increased before surgery in patients with aortic stenosis and remained increased early after surgery, although there was a 35% decrease. Late after AVR, muscle mass decreased significantly but remained slightly (P = NS) elevated. Left ventricular ejection fraction increased slightly after AVR. Left ventricular relaxation was significantly prolonged before surgery and returned toward normal early and late after AVR. Peak filling rates remained unchanged before and after surgery. Myocardial stiffness constant was increased before surgery in patients with aortic stenosis compared with controls and increased even further early after AVR but was normalized late after surgery. Muscle fiber diameter was elevated in patients with aortic stenosis before and after surgery compared with controls; however, it decreased significantly early and late after AVR with respect to preoperative data but remained hypertrophied even late after surgery. Interstitial fibrosis and fibrous contents were larger before surgery than in control subjects and increased even more early but decreased significantly late after AVR. CONCLUSIONS: Diastolic stiffness increases in aortic stenosis early after AVR parallel to the increase in interstitial fibrosis, whereas relaxation rate decreases with a reduction in left ventricular muscle mass. Late after AVR, both diastolic stiffness and relaxation are normalized due to the regression of both muscular and nonmuscular tissue. Thus, reversal of diastolic dysfunction in aortic stenosis takes years and is accompanied by a slow regression of interstitial fibrosis.

Adult↗
PubMed1997

[The extent of diastolic dysfunction and its correlation with subjective impairment of physical capacity in dilated cardiomyopathy].

OBJECTIVE: To find out whether in patients with dilated cardiomyopathy (DCM) there is a correlation between subjective reduction in physical capacity and the transmitral Doppler profile as a measure of left ventricular (LV) filling. PATIENTS AND METHODS: 30 consecutive patients (24 men, six women; average age 55 +/- 2 years) with chronic primary DCM were examined by Doppler echocardiography to determine possible differences in LV filling pattern, in correlation with subjective impairment of physical capacity graded according to the New York Heart Association (NYHA) classification. RESULTS: Mean LV ejection fraction was 34 +/- 1%. All patients were in sinus rhythm. Eight patients, in NYHA class I had nearly normal LV filling (E wave 79 m/s, A wave 0.76 m/s); 11 patients in class II had impaired relaxation (E wave 0.77 m/s. A wave 0.82 m/s) and 11 in class III/V had a restricted filling pattern (E wave 0.98 m/s. A wave 0.57 m/s). There was a significant difference between class II and class III/IV patients with regard to E wave deceleration time (0.15 and 0.11 s, respectively; P < 0.05), as well as between class I and class III/IV patients (0.18 and 0.11 s, respectively; P < 0.05). The A wave deceleration time was clearly shorter in class III/IV than class II (0.08 s and 0.11 s; P < 0.05) and class I patients (0.08 s and 0.10 s; P < 0.05). CONCLUSIONS: The extent of LV diastolic dysfunction correlated with subjective physical capacity. The more the LV filling pattern had changed from normal towards restricted, the greater the patient's symptoms.

Cardiomyopathy, Dilated↗
PubMed1998

Parasympathetic neuropathy associated with left ventricular diastolic dysfunction in patients with insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) may develop autonomic neuropathy (AN) and cardiac complications. The association between AN and cardiac dysfunction was assessed in 34 IDDM patients (age 40 years, diabetes duration 21 years, 15 women) by echocardiography/Doppler and autonomic nerve function tests. The expiration/inspiration ratio (E/I) was used to assess parasympathetic damage, and the acceleration and brake indices for assessment of sympathetic impairment. AN was present in 21 patients. Patients with abnormal E/I (n = 11) had lower E/A ratios than patients without AN; early to atrial peak filling ratio (E/Amax) was median 1.1 (inter-quartile range 0.2) vs 1.4 (0.7), p = 0.022; early to atrial integral filling ratio (E/Aintegral) was 1.7 (0.3) vs 2.3 (1.2), p = 0.006. Patients with AN and normal E/I (sympathetic neuropathy, n = 10) and patients without AN had similar E/A ratios. E/Aintegral was also lower in patients with abnormal E/I compared with patients with AN and normal E/I; 1.7 (0.3) vs 2.2 (0.7), p = 0.008. Systolic function and cardiac dimensions were generally unaffected and similar in the three groups. In conclusion, diastolic dysfunction and parasympathetic neuropathy are related in IDDM patients.

Adolescent↗
PubMed2003

Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure.

BACKGROUND: Angiotensin (Ang) II, which plays a crucial role in the cardiac remodeling process, is generated via angiotensin-converting enzyme (ACE); however, an alternative generation pathway, chymase, which is stored in the mast cells, also exists in the heart. Cardiac chymase is insensitive to ACE inhibitors (ACEIs), and heart chymase promotes interstitial fibrosis by affecting collagen metabolism via transforming growth factor-beta in vitro. Therefore, selective chymase blockade seems to be an important strategy in the prevention of cardiac remodeling METHODS AND RESULTS: We evaluated the effects of a specific chymase inhibitor, SUNC8257 (Chy I; 10 mg/kg twice a day; n=7), on changes in cardiac structures, Ang II levels, and gene expressions, which are characterized as molecular markers for fibrosis, in dogs with tachycardia induced heart failure (HF). In HF, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with the normal group; however, Chy I significantly decreased the mast cell density and cardiac Ang II levels. Despite no significant differences in LV systolic function compared with the vehicle group, Chy I decreased LV end-diastolic pressure and shortened the prolongation of tau. Chy I suppressed collagen-type I and III and transforming growth factor-beta mRNA levels and decreased fibrosis in the LV compared with the vehicle. CONCLUSIONS: The chymase pathway may be critical for cardiac diastolic dysfunction accompanied with fibrosis. Chronic chymase inhibition may therefore become an important strategy in the prevention of cardiac remodeling in HF.

Angiotensin II↗