Comparison of troponin and natriuretic peptides in Takotsubo syndrome and acute coronary syndrome: a meta-analysis.

OBJECTIVE: Takotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis. METHODS: We searched five literature databases for studies reporting NPs (Brain NP (BNP)/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients, respectively). RESULTS: Troponin was significantly lower in TTS than ACS (standardised mean difference (SMD) -0.86; 95% CI, -1.08 to -0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (×ULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 95% CI, 0.44 to 0.80; p<0.00001) and 5.8×ULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (95% CI, 0.70 to 0.93), and 0.92 (95% CI, 0.80 to 1.00) for ST-segment elevation myocardial infarction versus TTS. For NPs, AUC was 0.69 (95% CI, 0.48 to 0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive Partitioning and Regression Tree analysis calculated a troponin threshold ≥26×ULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57%, respectively, with 94.32% positive predictive value and 29.40% negative predictive value. CONCLUSIONS: Troponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin ≥26×ULN patients are far more likely to have ACS.

In vivo grafting of large engineered heart tissue patches for cardiac repair.

Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be a novel therapy for heart failure. EHTs restore cardiac function in rodent injury models, but more data are needed in clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm × 1.5 cm × 1.5 mm) consisting of up to 20 million human induced pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in a fibrin-based hydrogel was developed. A rabbit myocardial infarction model was then established to test for feasibility and efficacy. Our data showed that hPSC-CMs in EHTs became more aligned over 28 days and had improved contraction kinetics and faster calcium transients. Blinded echocardiographic analysis revealed a significant improvement in function in infarcted hearts that received EHTs, along with reduction in infarct scar size by 35%. Vascularization from the host to the patch was observed at week 1 and stable to week 4, but electrical coupling between patch and host heart was not observed. In vivo telemetry recordings and ex vivo arrhythmia provocation protocols showed that the patch was not pro-arrhythmic. In summary, EHTs improved function and reduced scar size without causing arrhythmia, which may be due to the lack of electrical coupling between patch and host heart.