Biventricular takotsubo cardiomyopathy with asymmetrical wall motion abnormality between left and right ventricle: a report of new case and literature review.

Takotsubo cardiomyopathy (TC) is characterized by transient wall motion abnormalities most commonly involving the left ventricle (LV). Although biventricular TC had been considered uncommon condition, recently biventricular TC has been reported as a new variant observed in 19-42% of all TC presentations. Since biventricular TC has a poor prognosis as compared with isolated TC, it is important to distinguish between isolated LV TC and biventricular TC. We present a case of 70-year-old female with dyspnea persisting for 2 days. Electrocardiogram showed symmetrical T-wave inversion in leads V2-V4. Transthoracic echocardiography (TTE) revealed diffuse hypo-kinesis except for the apical inferior LV and LV ejection fraction of 32%. Hyper-kinesis of the right ventricular (RV) basal segment and dys-kinesis of the RV apical segment. 2 weeks after admission, coronary angiography showed no evidence of significant stenosis. LV ejection fraction improved to 51% and wall motion abnormalities of the RV basal and apical segments were ameliorated to normo-kinesis. Electrocardiogram revealed symmetrical and deepened T-wave inversion in leads V2-V3. The presence of a transient abnormality in biventricular wall motion beyond a single coronary artery perfusion territory with new electrocardiographic change met the diagnostic criteria of definite TC defined by Mayo Clinic criteria. 4 weeks after admission, no recurrence of wall motion abnormalities in both ventricles were found and T-wave inversion ameliorated. To our knowledge, this is the first report of biventricular TC with asymmetrical abnormities of wall motion between LV and RV.

Cancer therapeutics-related cardiac dysfunction in a patient treated with abiraterone for castration-resistant prostate cancer.

Abiraterone is an agent effective for castration-resistant prostate cancer, but there have been no reports of cardiotoxic effects inducing cardiomyopathy, to our knowledge. We present a case of an 86-year-old man with castration-resistant prostate cancer treated with abiraterone. He had received an androgen receptor antagonist (bicalutamide) and a gonadotropin-releasing hormone antagonist (degarelix) for 3 years. These agents were changed to enzalutamide due to elevation of plasma prostate-specific antigen level of 129 ng/mL. One year later, the oral androgen receptor inhibitor (enzalutamide) caused drug-induced lung injury and was changed to abiraterone. Transthoracic echocardiography (TTE) revealed normal left ventricular systolic function, and left ventricular ejection fraction (LVEF) was 67%. Four weeks after administration of abiraterone, he complained of dyspnea on effort and bilateral leg edema, and he was diagnosed with heart failure. TTE showed hypokinesis of the diffuse LV, and LVEF decreased to 45%. The various causes of heart failure were excluded. Since a cardiotoxic effect of abiraterone was suspected, administration of abiraterone was discontinued. Two weeks after cessation of abiraterone, LVEF ameliorated to 57%, and then 5 months after cessation of abiraterone, LVEF further improved to 65%. To our knowledge, this is the first report of definite cancer therapeutics-related cardiac dysfunction due to a hormonal agent such as abiraterone diagnosed according to the American Society of Echocardiography and European Association of Cardiovascular Imaging criteria.

Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction.

BACKGROUND: Reperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. METHODS: Fifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6±13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringer's solution (20-30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. RESULTS: The mean corrected thrombolysis in myocardial infarction frame count was 20.1±10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751±2227IU/L and 276±181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. CONCLUSIONS: PCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy.

Distinct iPS Cells Show Different Cardiac Differentiation Efficiency.

Patient-specific induced pluripotent stem (iPS) cells can be generated by introducing transcription factors that are highly expressed in embryonic stem (ES) cells into somatic cells. This opens up new possibilities for cell transplantation-based regenerative medicine by overcoming the ethical issues and immunological problems associated with ES cells. Despite the development of various methods for the generation of iPS cells that have resulted in increased efficiency, safety, and general versatility, it remains unknown which types of iPS cells are suitable for clinical use. Therefore, the aims of the present study were to assess (1) the differentiation potential, time course, and efficiency of different types of iPS cell lines to differentiate into cardiomyocytes in vitro and (2) the properties of the iPS cell-derived cardiomyocytes. We found that high-quality iPS cells exhibited better cardiomyocyte differentiation in terms of the time course and efficiency of differentiation than low-quality iPS cells, which hardly ever differentiated into cardiomyocytes. Because of the different properties of the various iPS cell lines such as cardiac differentiation efficiency and potential safety hazards, newly established iPS cell lines must be characterized prior to their use in cardiac regenerative medicine.

Acute aortic regurgitation due to aortic dissection confined to the sinus of Valsalva.

A 34-year-old man with severe heart failure was diagnosed with acute aortic regurgitation (AR) by transthoracic echocardiography (TTE). However, this differential diagnosis was incomplete. Only transesophageal echocardiography (TEE) revealed an intimal flap, leading to a diagnosis of Stanford type A aortic dissection. No abnormal findings were observed in the ascending aorta by contrast-enhanced computed tomography (CT). Aortic dissection confined to the sinus of Valsalva has rarely been reported; however, TEE should still be considered for the differential diagnosis of acute AR, even if there is no evidence of dissection by TTE or contrast-enhanced CT.

Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway.

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.

Zac1 is an essential transcription factor for cardiac morphogenesis.

RATIONALE: The transcriptional networks guiding heart development remain poorly understood, despite the identification of several essential cardiac transcription factors. OBJECTIVE: To isolate novel cardiac transcription factors, we performed gene chip analysis and found that Zac1, a zinc finger-type transcription factor, was strongly expressed in the developing heart. This study was designed to investigate the molecular and functional role of Zac1 as a cardiac transcription factor. METHODS AND RESULTS: Zac1 was strongly expressed in the heart from cardiac crescent stages and in the looping heart showed a chamber-restricted pattern. Zac1 stimulated luciferase reporter constructs driven by ANF, BNP, or alphaMHC promoters. Strong functional synergy was seen between Zac1 and Nkx2-5 on the ANF promoter, which carries adjacent Zac1 and Nkx2-5 DNA-binding sites. Zac1 directly associated with the ANF promoter in vitro and in vivo, and Zac1 and Nkx2-5 physically associated through zinc fingers 5 and 6 in Zac1, and the homeodomain in Nkx2-5. Zac1 is a maternally imprinted gene and is the first such gene found to be involved in heart development. Homozygous and paternally derived heterozygous mice carrying an interruption in the Zac1 locus showed decreased levels of chamber and myofilament genes, increased apoptotic cells, partially penetrant lethality and morphological defects including atrial and ventricular septal defects, and thin ventricular walls. CONCLUSIONS: Zac1 plays an essential role in the cardiac gene regulatory network. Our data provide a potential mechanistic link between Zac1 in cardiogenesis and congenital heart disease manifestations associated with genetic or epigenetic defects in an imprinted gene network.