Myocardial Contraction Abnormalities Research Articles

Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies.

Studying monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combine patient-derived and genetically engineered iPSCs with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene Tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural, and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS “heart on chip” tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies, and advances iPSC-based in vitro modeling of cardiomyopathy.

Transient myocardial dysfunction after smoke inhalation

Acute onset, transient (reversible) myocardial contraction abnormality has been described in patients with acute non-cardiac illness and after acute emotional stress. Such reversible myocardial contraction abnormalities may occur via mechanisms other than reduction in epicardial coronary blood flow. We report a case of acute transient cardiomyopathy after smoke exposure. The patient developed acute heart failure without evidence of carbon monoxide poisoning that resolved within 4 days. An association between brief smoke exposure without carbon monoxide poisoning and acute heart failure has not been previously described.

Reversible Myocardial Contraction Abnormalities in Patients With an Acute Noncardiac Illness

Reversible myocardial contraction abnormalities are usually observed in patients with acute ischemic syndromes caused by coronary artery disease. In this study, we report the occurrence of reversible anterior-apical contraction abnormalities in patients with an acute noncardiac illness. This was a retrospective study of 22 patients with the following characteristics: (1) hospitalization for an acute noncardiac illness; (2) appearance of deep T-wave inversion in the precordial leads of the ECG; and (3) presence of an anterior wall motion abnormality on an echocardiogram. Standard clinical information was collected together with results of serial ECGs, echocardiograms, and coronary angiograms. The primary diagnoses for the 22 acutely ill patients included CNS injury (n=6); sepsis (n=3); acute pulmonary disease (n=3); drug overdose or metabolic abnormality (n=7); and post noncardiac surgery (n=3). An initial echocardiogram revealed an anterior apical wall motion abnormality. At follow-up, all patients had progressive improvement in anterior wall motion with return of normal wall motion in 16 patients (73%). All patients evolved deep T-wave inversion (average, 7.8 mm) and QT interval lengthening in the precordial leads. Coronary angiography revealed a significant stenosis in the likely culprit artery (left anterior descending) in only one patient. A reversible cardiac contraction abnormality of the anterior wall and apex of the left ventricle can complicate the clinical course of critically ill patients in the absence of significant coronary artery disease. This phenomenon is associated with striking T-wave inversion and QT interval lengthening. Mechanisms other than myocardial ischemia may lead to the occurrence of reversible regional myocardial contraction abnormalities.

Early assessment of coronary reserve after bypass surgery by dipyridamole transesophageal echocardiographic stress test

The evaluation of coronary reserve within a few hours of aortocoronary bypass surgery could be of extreme utility for the follow-up or therapeutical management of these patients. In 11 men patients who underwent aortocoronary bypass surgery, a dipyridamole echocardiography stress test was carried out before (1 to 3 days), early after (68 to 130 minutes), and 1 week after surgery. The first and third tests were performed using a standard transthoracic approach, while the second was performed by a transesophageal approach. Dipyridamole was administered intravenously at a dose of 0.56 mg/kg body weight (low dose) and eventually adding 0.28 mg/kg body weight (high dose), always in the absence of antiischemic therapy. An arbitrary wall motion score (0 = eukinesia; 1 = hypokinesia; 2 = akinesia; 3 = dyskinesia) was assigned to the seven different myocardial regions in which the left ventricle was divided in order to have a semiquantitative score. Under basal conditions wall motion score per patient in the three series of tests did not change significantly (1.6, 1.4, and 1.5, respectively), while the mean score during dipyridamole administration showed significant differences (3.6, 1.9, and 1.9, respectively), indicative of the results obtained by surgical repair. The test, positive in all patients before surgery, showed wall motion abnormalities and ischemic ECG changes in two patients immediately after surgery by the transesophageal approach. One patient who had a normal basal contraction pattern and an abnormal response after the test developed in the following days a perioperative myocardial infarction, while a second patient in the follow-up period developed low-level effort angina. Furthermore, by the transthoracic approach it was possible to document in three patients the reversibility of myocardial contraction abnormalities seen under basal conditions, the so-called “hibernating phenomenon.” It is worthwhile to stress that the results obtained by the test performed 1 week after surgery were the same as those obtained 2 hours after surgery, indicating that the changes in coronary circulation have stabilized by the early hours after surgery. In conclusion, our data, although preliminary, demonstrate that with the transesophageal approach it is possible to evaluate the changes induced by coronary bypass surgery even in the early phases, allowing better patient management and permitting risk stratification.

Cardiac output and regional myocardial contraction in anorexia nervosa

The study measured cardiac output and assessed regional myocardial contraction in 14 patients with anorexia nervosa, some of whom also had bulimia, and in 15 controls. The experimental and control groups were not significantly different in age or body surface area ( p = > 0.05). To evaluate regional myocardial contraction, 12 of 14 anorexia nervosa-bulimia (ANB) patients were studied in the acute phase and once serially at a mean interval of 1.5 years by assessing the movement of each left ventricular wall segment toward the center of the ventricle as imaged in the precordial short axis. Cardiac output was measured in the ascending aorta by pulsed Doppler for control subjects and for 13 ANB patients. Regional myocardial contraction was normal for all controls, but eight of 14 ANB patients showed regional myocardial contraction abnormalities. Between studies, four of these eight demonstrated improved regional myocardial contraction, three remained unchanged, and one was worse. Mean cardiac output was markedly reduced in ANB patients (2.6 L/min) compared to controls (4.5 L/min) ( p = < 0.001). The low cardiac output in ANB patients was reflected as reduced mean ascending aortic velocity/second (18.5 cm/s) compared to a mean of 22.8 cm/s for controls ( p = < 0.02). Mean ascending aortic area was slightly smaller for ANB patients. Mean peak ascending aortic velocity was significantly lower in ANB patients than in controls ( p = < 0.02). Mitral valve prolapse was seen during at least one examination in seven of 14 ANB patients (0/15 controls) and disappeared in two of three patients following hydration. We condlude that ANB patients may have significant long-term abnormalities in cardiac output and regional myocardial contraction.

Late effects of coronary reperfusion on regional left ventricular function. Can infarct size be estimated noninvasively?

The prognosis of patients with acute myocardial infarction is related to the infarction size. We evaluated the ability of a clinical technique, two-dimensional echocardiography, to assess infarct size based on the extent of regional contraction abnormalities. Conscious closed-chest dogs with preplaced coronary snares underwent permanent coronary occlusion. The animals were studied by two-dimensional echo 20 min and 2 days after occlusion. The extent of myocardial contraction abnormalities (systolic wall thinning instead of normal systolic thickening) was correlated with the infarct size determined pathologically. Some dogs had pressure-induced left ventricular hypertrophy. Extent of regional contraction abnormalities demonstrated by two-dimensional echo correlated well with infarct size both early (20 min) (r = 0.92) and late (2 days) (r = 0.94) after permanent coronary occlusion. Dyskinesis extent modestly overestimated the infarct size. The relationship between dyskinesis and infarct size were similar in both normal and left ventricular hypertrophied hearts. We then undertook a study to assess the effects of coronary reperfusion on dyskinesis-infarct size relationships. Conscious, closed-chest dogs underwent 1-2 h of coronary occlusion followed by 2-10 days of coronary reperfusion. Significant regional dyskinesis was present after 1-2 h of occlusion and decreased by 50-60% of the occlusion value after 2 days of reperfusion without further change in extent of dyskinesis between 2 and 10 days of reperfusion. Of importance, however, was that there was no significant correlation between infarct size and extent of regional dyskinesis by two-dimensional echo after reperfusion, either after 2 days (r = 0.09) or 10 days (r = 0.29) of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography in experimentally-induced myocardial ischemia

Using an experimental canine model, we have employed echocardiography to study segmental dyskinesis produced by acute coronary occlusion. Characteristic alterations in posterior wall and septal motion occur after acute coronary ligation; these resemble clinical abnormalities described in acute and old myocardial infarction. The degree of dyskinesis produced is directly related to the severity of the perfusion deficit. Coronary reperfusion had variable effects on dyskinesis; most animals showed improvement but in some the myocardial contraction abnormalities became more severe. A variety of interventions were undertaken during ischemia. The elevated level of arterial pressure induced by the administration of methoxamine increased ventricular diameter and presumably oxygen requirements, and was deleterious to ischemic wall motion whereas the administration of norepinephrine reduced ventricular diameter and improved function. Intra-aortic balloon counterpulsation had little effect on either ischemic motion or perfusion. These experimental studies generally support conclusions drawn from clinical echocardiograms about the relationship of abnormalities of wall motion to coronary artery lesions and myocardial ischemia, and suggest further clinical uses for echocardiography in coronary disease.