Coronary Spasm and Polymorphic Ventricular Tachycardia One Year After Takotsubo.

Stress cardiomyopathy is typically considered to be a disease with a favorable long-term prognosis, with malignant arrhythmias accompanying only the acute phase. We describe a 51-year-old female who presented with palpitations one year after stress cardiomyopathy and complete recovery of apical left ventricular wall motion. Coronary spasm was strongly suspected based on transient ST-segment elevations followed by sustained polymorphic ventricular tachycardia captured on ambulatory Holter. Contrast injection during coronary angiography reproduced spasm and ventricular arrhythmia that resolved with intracoronary nitroglycerine. The patient was intolerant to nitrates therefore discharged on 2 calcium channel blockers. Shared decision was made to implant cardioverter defibrillator.

Malignant pericardial effusion with cardiac tamponade in ovarian adenocarcinoma.

BACKGROUND: Malignant pericardial effusion with cardiac tamponade is an uncommon metastatic manifestation of gynecologic cancers. We describe a patient with ovarian cancer who developed pericardial effusion with cardiac tamponade and was successfully treated with pericardiocentesis and intrapericardial instillation of thiotepa. CASE: A 52-year-old woman with stage IV ovarian adenocarcinoma presented with worsening cough, dyspnea, and fatigue. Chest X-ray and echocardiogram confirmed the presence of pericardial effusion with cardiac tamponade. Pericardial fluid cytology revealed adenocarcinoma. Treatment consisted of pericardiocentesis with thiotepa sclerotherapy. She survived 12 months post-therapy without recurrent pericardial tamponade. CONCLUSION: Patients with gynecologic cancers may develop a pericardial effusion with cardiac tamponade. Malignant pericardial effusion should be included in the differential diagnosis in patients with recurrent ovarian cancer who present with cardiac tamponade.

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure.

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease.

Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy. Preservation of systolic function.

Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that transduces hypertrophic stimuli to regulate transcriptional control of myocyte transformation. It is not known whether overexpression of MCIP1, a recently described endogenous inhibitor of calcineurin, impacts the hypertrophic response to pathophysiologically relevant pressure overload. Further, the functional consequences of calcineurin inhibition by MCIP1 under conditions of hemodynamic stress are unknown. Transgenic mice expressing a human cDNA encoding hMCIP1 in the myocardium were subjected to thoracic aortic banding. Transgenic mice and wild type littermates tolerated pressure overload equally well. Wild type mice developed left ventricular hypertrophy, but the hypertrophic response in transgenics was significantly blunted. An isoform of MCIP1 transcript was up-regulated by pressure stress, whereas MCIP2 transcript was not. Expression patterns of fetal genes were differentially regulated in banded MCIP1 hearts compared with wild type. Echocardiography performed at 3 weeks and 3 months revealed preservation of both left ventricular size and systolic function in banded MCIP1 mice despite the attenuated hypertrophic response. These data demonstrate attenuation of hypertrophic transformation when calcineurin is inhibited by MCIP1. Further, these data suggest that activation of hypertrophic marker genes may not be directly dependent on calcineurin activity. Finally, they demonstrate that ventricular performance is preserved despite attenuation of compensatory hypertrophy.