Letizia Spinelli

Relation Between Diastolic Perfusion Time and Coronary Artery Stenosis During Stress-Induced Myocardial Ischemia

BACKGROUND Experimental studies have demonstrated that during stress-induced myocardial ischemia, coronary obstruction and diastolic perfusion time are factors that limit subendocardial perfusion and correlate to degree of myocardial dysfunction. The relation between these two factors has not yet been investigated in humans. The aim of the present study was to assess the relation between diastolic perfusion time and degree of coronary stenosis during different types of stress tests. METHODS AND RESULTS Nine patients with isolated and proximal stenosis of the left anterior descending coronary artery were selected. Patients underwent three different randomized stress tests (upright, supine bicycle stress test, and transesophageal atrial pacing). Diastolic perfusion time, heart rate (RR interval), and systolic and diastolic pressures were measured during the test and at the ischemic threshold (0.1-mV ST-segment depression). Angiographic measurements of coronary stenosis were evaluated by quantitative coronary angiography. At the ischemic threshold, significant differences among tests were found in heart rate (P < .05), systolic pressure (P < .001), and diastolic pressure (P < .05). In each stress test, diastolic perfusion time at the ischemic threshold was closely correlated with minimal stenosis diameter (r = .97; P < .001) and percent diameter stenosis (r = .92; P < .001) with no difference among the tests. In contrast, heart rate, rate-pressure product, and time to ischemic threshold were not significantly correlated with percent diameter stenosis and minimal stenosis diameter. No significant correlation was observed at the ischemic threshold between diastolic perfusion time and corresponding values of heart rate, despite the close correlation at rest (r = .95; P < .001). CONCLUSIONS Despite differences in associated hemodynamic responses to various stress tests, a close relation exists between stenosis severity and diastolic perfusion time at the onset of stress-induced myocardial ischemia. Therefore, diastolic perfusion time at the ischemic threshold may be an indirect estimate of the hemodynamic significance of coronary stenosis.

Reversal of acromegalic cardiomyopathy in young but not in middle‐aged patients after 12 months of treatment with the depot long‐acting somatostatin analogue octreotide

background Cardiovascular disease is the most frequent cause of death of patients with acromegaly.

L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome.

Altered response to acute catecholamine increase in the synaptic cleft is considered to be the mechanism underlying transient left ventricular apical ballooning syndrome (LVABS). –3 Cardiac adrenergic receptors (ARs) of the b1 and b2 subtypes activate myocytes by coupling to the Ga subunit of the heterotrimeric Gs protein, but on the other hand they also promote G protein coupled receptor kinase (GRK)-mediated phosphorylation of bAR with the intent to shut-off signalling. The impact on cardiac function of genetic variants of molecules involved in the intracellular pathways of bAR signalling has been extensively investigated. –8

Left ventricular mass and function in children with GH deficiency before and during 12 months GH replacement therapy

objective  This open, prospective study was designed to evaluate the effect of GH deficiency (GHD) on left ventricular (LV) mass (LVM) and performance, by echocardiography, and on lipid profile during childhood.

Effects of enzyme replacement therapy in patients with Anderson-Fabry disease: a prospective long term cardiac magnetic resonance imaging study

Background: Anderson–Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. Objective: This study aimed to assess the long-term effects of ERT with recombinant α-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson–Fabry disease. Patients: Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson–Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). Results: At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Conclusions: Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson–Fabry disease.

G Protein-Coupled Receptor Kinase 2 in Patients With Acute Myocardial Infarction

Lymphocyte G protein-coupled receptor kinase 2 (GRK2) levels are increased in patients with chronic heart failure, and in this condition, they correlate with cardiac function. The aim of this study was to assess the prognostic role of GRK2 during acute cardiac dysfunction in humans. A study was designed to investigate the role of GRK2 levels in patients with acute coronary syndromes. Lymphocyte GRK2 levels were examined at admission and after 24 and 48 hours in 42 patients with acute coronary syndromes, 32 with ST-segment elevation myocardial infarction and 10 with unstable angina as a control group. Echocardiographic parameters of systolic and diastolic function and left ventricular remodeling were evaluated at admission and after 2 years. GRK2 levels increased during ST-segment elevation myocardial infarction and were associated with worse systolic and diastolic function. This association held at 2-year follow-up, when GRK2 was correlated with the ejection fraction and end-systolic volume, indicating a prognostic value for GRK2 levels during acute ST-segment elevation myocardial infarction. In conclusion, lymphocyte GRK2 levels increase during acute myocardial infarction and are associated with worse cardiac function. Taken together, these data indicate that GRK2 could be predictive of ventricular remodeling after myocardial infarction and could facilitate the tailoring of appropriate therapy for high-risk patients.

Cardiac autonomic responses to volume overload in normal subjects and in patients with dilated cardiomyopathy.

This study evaluated the effects of acute isotonic volume expansion on heart rate variability (HRV) in 10 patients with dilated cardiomyopathy (DCM) and in 10 age- and sex-matched normal volunteers. Echocardiographic left ventricular volumes and HRV measurements by continuous Holter recording were assessed at baseline, at 60 and 120 min during intravenous saline load (0.9% NaCl, 0.25 ml. kg(-1). min(-1)), and 60 min after infusion was terminated. Data analysis was performed by repeated-measures ANOVA. After volume expansion, left ventricular ejection fraction increased (F = 9.8; P < 0.001) in normal subjects and decreased (F = 8.7; P < 0.001) in DCM patients. During volume expansion a significant difference was also detectable between the two groups in root-mean-square successive difference (F = 25.2; P < 0.001), percentage of differences between successive normal R-R intervals >50 ms (F = 97.6; P < 0.001), high-frequency power (F = 50.1; P < 0.001), and low-frequency power (F = 41.6; P < 0.001), all of which reflect parasympathetic modulation of heart rate; in fact, these measurements increased in normal subjects and decreased in DCM patients. In normal subjects, the increase in HRV measurements during volume expansion suggests a parasympathetic activation, mediated by stimulation of cardiopulmonary and arterial mechanoreceptors. On the contrary, in DCM patients the parasympathetic withdrawal, already detectable at baseline, increases during volume expansion.This study evaluated the effects of acute isotonic volume expansion on heart rate variability (HRV) in 10 patients with dilated cardiomyopathy (DCM) and in 10 age- and sex-matched normal volunteers. Echocardiographic left ventricular volumes and HRV measurements by continuous Holter recording were assessed at baseline, at 60 and 120 min during intravenous saline load (0.9% NaCl, 0.25 ml ⋅ kg-1 ⋅ min-1), and 60 min after infusion was terminated. Data analysis was performed by repeated-measures ANOVA. After volume expansion, left ventricular ejection fraction increased ( F = 9.8; P < 0.001) in normal subjects and decreased ( F = 8.7; P < 0.001) in DCM patients. During volume expansion a significant difference was also detectable between the two groups in root-mean-square successive difference ( F = 25.2; P < 0.001), percentage of differences between successive normal R-R intervals >50 ms ( F = 97.6; P < 0.001), high-frequency power ( F = 50.1; P < 0.001), and low-frequency power ( F = 41.6; P < 0.001), all of which reflect parasympathetic modulation of heart rate; in fact, these measurements increased in normal subjects and decreased in DCM patients. In normal subjects, the increase in HRV measurements during volume expansion suggests a parasympathetic activation, mediated by stimulation of cardiopulmonary and arterial mechanoreceptors. On the contrary, in DCM patients the parasympathetic withdrawal, already detectable at baseline, increases during volume expansion.

Subtle Alterations of Cardiac Performance in Children with Growth Hormone Deficiency: Results of a Two-Year Prospective, Case-Control Study

BACKGROUND GH-deficient (GHD) children have reduced left ventricular (LV) mass, but impairment of cardiac function has never been documented. AIM The aim of the study was to evaluate effects of GHD and GH therapy on cardiac function using load-dependent and load-independent indices of myocardial contractility. PATIENTS AND METHODS Echocardiography was performed in 24 GHD children at baseline and 1 and 2 yr after GH therapy and in 24 controls. RESULTS Compared with controls, GHD children at baseline had lower LV mass (LV mass/BSA 50.6 +/- 1.8 vs. 60.5 +/- 2.4 g/m(2); P < 0.002, and LV mass/H(2.7) 28.7 +/- 1.2 vs. 33.6 +/- 1.3 g/m(2.7); P < 0.009). Global systolic function was normal, with only a trend toward slight impairment of the fractional shortening (34.9 +/- 1.5 vs. 37.6 +/- 1.1%). However, subtle LV dysfunction was revealed by load-dependent and load-independent indices of myocardial contractility. In fact, GHD patients compared with controls showed lower rate-corrected mean velocity of circumferential fiber shortening (1.0 +/- 0.03 vs. 1.18 +/- 0.03 circ/sec; P = 0.0001) and stress shortening index (0.10 +/- 0.02 vs. 0.18 +/- 0.02; P < 0.007) and higher end-systolic stress (49.2 +/- 1.4 vs. 45.7 +/- 1.0 g/cm(2); P < 0.05). One year of GH treatment was associated with a significant improvement of cardiac size (LV mass/BSA 67.8 +/- 2.9 g/m(2); LV mass/H(2.7) 38.2 +/- 2.0 g/m(2.7); P < 0.0001 and P = 0.0003, respectively) and myocardial contractility (mean velocity of circumferential fiber shortening 1.2 +/- 0.04 circ/sec; P < 0.0002; stress shortening index 0.19 +/- 0.02; P < 0.003) and reduced afterload (end-systolic stress 43.9 +/- 1.4 g/cm(2); P < 0.03). CONCLUSIONS Our data indicate that GH deficiency is associated with abnormalities in morphology and function in not only adults but also children and further supports the beneficial effect of GH on the heart.

Effects of exercise training started within 2 weeks after acute myocardial infarction on myocardial perfusion and left ventricular function: a gated SPECT imaging study

Background: Several studies suggested that exercise training might improve myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. However, these findings were obtained in patients with chronic coronary artery disease using thallium-201 myocardial perfusion scintigraphy. We evaluated whether a long-term exercise-based cardiac rehabilitation (CR) started early (9 ± 3 days) after ST elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function, evaluated by gated single-photon emission computed tomography (SPECT) imaging. Design: Randomized controlled study. Methods: Fifty patients with recent STEMI were randomized into two groups: 24 enrolled in a 6-month exercise-based CR programme (group T) and 26 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and gated SPECT within 3 weeks after STEMI and at 6-month follow up. Results: At follow up, group T showed a significant reduction of stress-induced ischaemia (p < 0.01) and an improvement in resting and post-stress wall motion (both p < 0.005) and resting (p < 0.05) and post-stress wall thickness (p < 0.005) score indexes. At follow up, group T showed an improvement in peak oxygen consumption (p < 0.0001), O2 pulse (p < 0.05), and in the slope of increase in ventilation over carbon dioxide output (p < 0.001). No changes in myocardial perfusion parameters, LV function, and cardiopulmonary indexes were observed in group C at follow up. Conclusions: Six months of exercise training early after STEMI reduces stress-induced ischaemia and improves LV wall motion and thickness. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with the improvement of cardiovascular functional capacity.

Cardiovascular Complications in Acromegaly: Methods of Assessment

Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.