Numerous studies have reported correlations between plasma microRNA signatures and cardiovascular disease. MicroRNA-133a (Mir-133a) has been researched extensively for its diagnostic value in acute myocardial infarction (AMI). While initial results seemed promising, more recent studies cast doubt on the diagnostic utility of Mir-133a, calling its clinical prospects into question. Here, the diagnostic potential of Mir-133a was analyzed using data from multiple papers. Medline, Embase, and Web of Science were systematically searched for publications containing “Cardiovascular Disease”, “MicroRNA”, “Mir-133a” and their synonyms. Diagnostic performance was assessed using area under the summary receiver operator characteristic curve (AUC), while examining the impact of age, sex, final diagnosis, and time. Of the 753 identified publications, 9 were included in the quantitative analysis. The pooled AUC for Mir-133a was 0.73. Analyses performed separately on studies using healthy vs. symptomatic controls yielded pooled AUCs of 0.89 and 0.68, respectively. Age and sex were not found to significantly affect diagnostic performance. Our findings indicate that control characteristics and methodological inconsistencies are likely the causes of incongruent reports, and that Mir-133a may have limited use in distinguishing symptomatic patients from those suffering AMI. Lastly, we hypothesized that Mir-133a may find a new use as a risk stratification biomarker in patients with specific subsets of non-ST elevation myocardial infarction (NSTEMI).

Objective: Hypertension is the leading cause of cardiovascular disease and premature death. New methods for early detection of hypertension and its consequences can reduce complications arising from uncontrolled hypertension. Pulse-wave velocity (PWV), a measure of arterial stiffness, has been recognized as a valuable tool in assessing risk for cardiovascular complications, although its use in clinical practice is currently limited. Here we examine whether brachial--ankle PWV (baPWV) and femoral--ankle PWV (faPWV) are elevated in nonhypertensive volunteers, with and without a history of familial hypertension. Methods: Volunteers were recruited and questioned as to their medical background and family history. Participants were divided into two groups based on history of familial hypertension and were measured for baPWV and faPWV. Carotid--femoral PWV was computed from these measurements. Results: A total of 82 healthy nonhypertensive volunteers (mean age 31.4 ± 9.6) were recruited. Among the study cohort, 43.7% had a history of familial hypertension. There were no between-group differences in any other clinical or demographic characteristics. Both baPWV and faPWV were significantly elevated in volunteers with a history of familial hypertension (10.86 ± 1.69 vs. 9.68 ± 1.52 m/s, P < 0.004, and 7.01 ± 1.65 vs. 6.28 ± 1.26 m/s, P < 0.028, respectively). Conclusion: Volunteers with a history of familial hypertension present with elevated baPWV and faPWV. This is suggestive of increased central and peripheral arterial stiffness in susceptible individuals before the onset of hypertension. Routine measurement of these parameters may allow for early intervention and risk stratification, especially in persons with a history of familial hypertension.

Introduction: Current models used to investigate reentrant arrhythmias allow for limited control of arrhythmia parameters and morphology. Here, we developed a method for the induction of morphologically and physiologically defined arrhythmias using human induced pluripotent stem cell derived cardiac cell sheets (hiPSC-CCSs) and optogenetic tools. Methods: One million hiPSC-cardiomyocytes expressing the optogenetic channel CoChR were used to create the hiPSC-CCSs. Rotor illumination patterns were generated either by computer-aided design or by utilizing previously recorded rotor patterns. A digital micro mirror device (DMD) and a 470nm LED were used to project five complete cycles of these rotor patterns onto the hiPSC-CCSs. Results: Optical projection of typical rotors led to repeated development of arrhythmias in all sampled tissues (n=11). The resulting arrhythmias resembled the projected rotor patterns in terms of directionality (clockwise or counterclockwise) and number of cores ,and were highly reproducible for each projection (Fig.1A). Interestingly, we identified a minimal and maximal frequency of the projected rotor that could induce arrhythmias (Fig.1B). Moreover, the frequency of the generated rotor could not be increased beyond a certain value despite further increases in the projected rotor frequency (Fig.1B). Lastly, to assess the effects of tissue EP properties, the process was repeated after treatment with the IKr blocker E-4031 (30nM). E-4031 treatment significantly reduced the minimal and maximal frequencies of the projected rotor that could still induce arrhythmia and slowed the maximal frequency of the resulting rotor (Fig.1B). Conclusions: We present a new method for the optical induction of reentrant arrhythmias allowing the generation of rotors rapidly, reproducibly, and with a predesigned morphology. This approach may allow for a paradigm shift in the way reentrant arrhythmias are studied.

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