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Introduction: Right ventricular failure (RVF) remains a major cause of morbidity and mortality after continuous flow Left Ventricle Assist Device (CF-LVAD) implantation. Previous risk assessments using pre-operative data to predict RVF have performed only modestly well. Methods: We retrospectively studied the potential of echocardiographic RV dP/dt - a non-invasive measure of right ventricular contractility derived from the Doppler signal of tricuspid regurgitation, to predict post-LVAD RVF in patients who were inotrope-independent and those who were on inotropic therapy prior to LVAD. Sixty-five consecutive CF-LVAD recipients at Vanderbilt University Medical Center from 2013-2019 who had a baseline echocardiogram without inotrope support within 3 months prior to LVAD implantation were included. Forty patients from the cohort were started on inotropes prior to LVAD implantation. Baseline off-inotrope and on-inotrope RV dP/dt data were analyzed. Severity of post-LVAD RVF was defined by INTERMACS criteria. Results: Of the 65 studied patients, 30 patients had none or mild RVF, 17 had moderate RVF, and 18 had severe RVF. Patients with severe RVF had markedly poorer survival outcome than no/mild and moderate RVF patients. Baseline RV dP/dt was significantly lower in patients who developed post-LVAD severe RVF. A baseline off-inotrope, or on-inotrope RV dP/dt ≥ 300 mmHg/s predicted a low risk of severe RVF with high sensitivity (89% and 80%, respectively) and negative predictive value (91% and 88% respectively); while the presence of both off-inotrope and on-inotrope RV dP/dt < 300 mmHg/s was associated with a high likelihood of post-LVAD RVF (OR 10.5, 95% 1.8-59.4 compared to the rest of the cohort on inotrope therapy). Conclusion: Echocardiographic RV dP/dt may be a valuable adjunct tool for prediction of post-LVAD severe RVF in patients undergoing evaluation for LVAD implantation.

Background— Activation of cellular Ca 2+ signaling molecules appears to be a fundamental step in the progression of cardiomyopathy and arrhythmias. Myocardial overexpression of the constitutively active Ca 2+ -dependent phosphatase calcineurin (CAN) causes severe cardiomyopathy marked by left ventricular (LV) dysfunction, arrhythmias, and increased mortality rate, but CAN antagonist drugs primarily reduce hypertrophy without improving LV function or risk of death. Methods and Results— We found that activity and expression of a second Ca 2+ -activated signaling molecule, calmodulin kinase II (CaMKII), were increased in hearts from CAN transgenic mice and that CaMKII-inhibitory drugs improved LV function and suppressed arrhythmias. We devised a genetic approach to “clamp” CaMKII activity in CAN mice to control levels by interbreeding CAN transgenic mice with mice expressing a specific CaMKII inhibitor in cardiomyocytes. We developed transgenic control mice by interbreeding CAN transgenic mice with mice expressing an inactive version of the CaMKII-inhibitory peptide. CAN mice with CaMKII inhibition had reduced risk of death and increased LV and ventricular myocyte function and were less susceptible to arrhythmias. CaMKII inhibition did not reduce transgenic overexpression of CAN or expression of endogenous CaMKII protein or significantly reduce most measures of cardiac hypertrophy. Conclusions— CaMKII is a downstream signal in CAN cardiomyopathy, and increased CaMKII activity contributes to cardiac dysfunction, arrhythmia susceptibility, and longevity during CAN overexpression.

Introduction: Takotsubo’s cardiomyopathy, or stress induced cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. It is seen more commonly in post-menopausal women and is usually preceded by an acute medical illness or intense emotional or physical stress. While the Mayo Criteria for the classification of Takotsubo’s cardiomyopathy involves the absence of epicardial coronary disease, up to 10% of patients have been found to have concurrent significant coronary artery disease. Conclusions: We present a case of a patient who presented with seizures and was found to have ST elevations, elevated cardiac enzymes and a new cardiomyopathy. While it was discovered that she had severe coronary disease of her LAD and RCA, the true nature of her cardiomyopathy and presentation was a stress-induced cardiomyopathy in the setting of seizure. The accuracy of this diagnosis affected the prognosis and treatment options for our patient. Cardiac MRI, and specifically the presence or absence of late gadolinium enhancement, helped differentiate the etiology of her cardiomyopathy. With the increasing prevalence of coronary disease, we will likely see more cases such as these in the future and should continue to evolve our definition and tools for the diagnosis of an increasing and interesting phenomenon.

Background— Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy. Methods and Results— One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis. The 2 groups were similar in terms of clinical and early echocardiographic characteristics. Mean left ventricular ejection fraction (LVEF) was 31%, and moderate or greater mitral regurgitation (MR) was noted in 39.1%. On multivariate analysis, the only independent predictors of survival were MR severity and LVEF. A survival benefit for the ERV strategy was observed at all levels of LVEF and MR. Conclusions— A wide range of cardiac structural and functional abnormalities exists in patients presenting with acute cardiogenic shock. Both short- and long-term mortality appear to be associated with initial left ventricular systolic function and MR as assessed by echocardiography, and a benefit of ERV is noted regardless of baseline LVEF or MR.