Apical ballooning syndrome complicated by acute severe mitral regurgitation with left ventricular outflow obstruction – Case report

BACKGROUND: Apical ballooning syndrome (or Takotsubo cardiomyopathy) is a syndrome of transient left ventricular apical ballooning. Although first described in Japanese patients, it is now well reported in the Caucasian population. The syndrome mimicks an acute myocardial infarction but is characterised by the absence of obstructive coronary disease. We describe a serious and poorly understood complication of Takotsubo cardiomyopathy. CASE PRESENTATION: We present the case of a 65 year-old lady referred to us from a rural hospital where she was treated with thrombolytic therapy for a presumed acute anterior myocardial infarction. Four hours after thrombolysis she developed acute pulmonary oedema and a new systolic murmur. It was presumed she had acute mitral regurgitation secondary to a ruptured papillary muscle, ischaemic dysfunction or an acute ventricular septal defect. Echocardiogram revealed severe mitral regurgitation, left ventricular apical ballooning, and systolic anterior motion of the mitral valve with significant left ventricular outflow tract gradient (60–70 mmHg). Coronary angiography revealed no obstructive coronary lesions. She had an intra-aortic balloon pump inserted with no improvement in her parlous haemodynamic state. We elected to replace her mitral valve to correct the outflow tract gradient and mitral regurgitation. Intra-operatively the mitral valve was mildly myxomatous but there were no structural abnormalities. She had a mechanical mitral valve replacement with a 29 mm St Jude valve. Post-operatively, her left ventricular outflow obstruction resolved and ventricular function returned to normal over the subsequent 10 days. She recovered well. CONCLUSION: This case represents a serious and poorly understood association of Takotsubo cardiomyopathy with acute pulmonary oedema, severe mitral regurgitaton and systolic anterior motion of the mitral valve with significant left ventricular outflow tract obstruction. The sequence of our patient's presentation suggests that the apical ballooning caused geometric alterations in her left ventricle that in turn led to acute and severe mitral regurgitation, systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction. The left ventricular outflow tract obstruction and mitral regurgitation were corrected by mechanical mitral valve replacement. We describe a variant of Takotsubo cardiomyopathy with acute mitral regurgitation, systolic anterior motion of the mitral valve leaflet and left ventricular outflow tract obstruction of a dynamic nature

Bronchopulmonary dysplasia prediction models: a systematic review and meta-analysis with validation

IntroductionPrediction models could identify infants at the greatest risk of bronchopulmonary dysplasia (BPD) and allow targeted preventative strategies. We performed a systematic review and meta-analysis with external validation of identified models. Methods Studies using predictors available before day 14 of life to predict BPD in very preterm infants were included. Two reviewers assessed 7,628 studies for eligibility. Meta-analysis of externally validated models was followed by validation using 62,864 very preterm infants in England and Wales.Results64 studies using 53 prediction models were included totalling 274,407 infants (range 32–156,587/study). 35 (55%) studies predated 2010; 39 (61%) were single-centre studies. 97% of studies had a high risk of bias, especially in the analysis domain. Following meta-analysis of 22 BPD and 11 BPD/death composite externally validated models, Laughon’s day one model was the most promising in predicting BPD and death (C-statistic 0.76 (95% CI 0.70–0.81) and good calibration). Six models were externally validated in our cohort with C-statistics between 0.70–0.90 but with poor calibration.ConclusionFew BPD prediction models were developed with contemporary populations, underwent external validation, or had calibration and impact analyses. Contemporary, validated, and dynamic prediction models are needed for targeted preventative strategies

Takotsubo cardiomyopathy in a Caucasian Italian woman: Case report

BACKGROUND: Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levels CASE PRESENTATION: A 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2–V3 and ST-segment depression in leads V5–V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities. CONCLUSION: Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman

Responsible research for the construction of maximally humanlike automata: the paradox of unattainable informed consent

Since the Nuremberg Code and the first Declaration of Helsinki, globally there has been increasing adoption and adherence to procedures for ensuring that human subjects in research are as well informed as possible of the study’s reasons and risks and voluntarily consent to serving as subject. To do otherwise is essentially viewed as violation of the human research subject’s legal and moral rights. However, with the recent philosophical concerns about responsible robotics, the limits and ambiguities of research-subjects ethical codes become apparent on the matter of constructing automata that maximally resemble human beings (as defined hereunder). In this case, the automata themselves, as products of research and development, are in the very process of their construction subjects of research and development. However, such research faces a paradox: The subjects cannot give their informed consent to this research for their own development, although their consent would be needed for the research. According to ethical codes, this research would be unethical. The article then explores whether the background concepts giving rise to this paradox could be reframed in order to allow such research to proceed ethically

Stress-related cardiomyopathies

Stress-related cardiomyopathies can be observed in the four following situations: Takotsubo cardiomyopathy or apical ballooning syndrome; acute left ventricular dysfunction associated with subarachnoid hemorrhage; acute left ventricular dysfunction associated with pheochromocytoma and exogenous catecholamine administration; acute left ventricular dysfunction in the critically ill. Cardiac toxicity was mediated more by catecholamines released directly into the heart via neural connection than by those reaching the heart via the bloodstream. The mechanisms underlying the association between this generalized autonomic storm secondary to a life-threatening stress and myocardial toxicity are widely discussed. Takotsubo cardiomyopathy has been reported all over the world and has been acknowledged by the American Heart Association as a form of reversible cardiomyopathy. Four "Mayo Clinic" diagnostic criteria are required for the diagnosis of Takotsubo cardiomyopathy: 1) transient left ventricular wall motion abnormalities involving the apical and/or midventricular myocardial segments with wall motion abnormalities extending beyond a single epicardial coronary artery distribution; 2) absence of obstructive epicardial coronary artery disease that could be responsible for the observed wall motion abnormality; 3) ECG abnormalities, such as transient ST-segment elevation and/or diffuse T wave inversion associated with a slight troponin elevation; and 4) the lack of proven pheochromocytoma and myocarditis. ECG changes and LV dysfunction occur frequently following subarachnoid hemorrhage and ischemic stroke. This entity, referred as neurocardiogenic stunning, was called neurogenic stress-related cardiomyopathy. Stress-related cardiomyopathy has been reported in patients with pheochromocytoma and in patients receiving intravenous exogenous catecholamine administration. The role of a huge increase in endogenous and/or exogenous catecholamine level in critically ill patients (severe sepsis, post cardiac resuscitation, post tachycardia) to explain the onset of myocardial dysfunction was discussed. Further research is needed to understand this complex interaction between heart and brain and to identify risk factors and therapeutic and preventive strategies

Xenograft models of head and neck cancers

Head and neck cancers are among the most prevalent tumors in the world. Despite advances in the treatment of head and neck tumors, the survival of patients with these cancers has not markedly improved over the past several decades because of our inability to control and our poor understanding of the regional and distant spread of this disease. One of the factors contributing to our poor understanding may be the lack of reliable animal models of head and neck cancer metastasis. The earliest xenograft models in which human tumor cells were grown in immunosuppressed mice involved subcutaneous implantation of human head and neck cancer cell lines. Subcutaneous xenograft models have been popular because they are easy to establish, easy to manage, and lend themselves to ready quantitation of the tumor burden. More recently, orthotopic xenograft models, in which the tumor cells are implanted in the tumor site of origin, have been used with greater frequency in animal studies of head and neck cancers. Orthotopic xenograft models are advantageous for their ability to mimic local tumor growth and recapitulate the pathways of metastasis seen in human head and neck cancers. In addition, recent innovations in cell labeling techniques and small-animal imaging have enabled investigators to monitor the metastatic process and quantitate the growth and spread of orthopically implanted tumors. This review summarizes the progress in the development of murine xenograft models of head and neck cancers. We then discuss the advantages and disadvantages of each type of xenograft model. We also discuss the potential for these models to help elucidate the mechanisms of regional and distant metastasis, which could improve our ability to treat head and neck cancers