Unraveling a rare presentation of bivalvular infective endocarditis using POCUS.

Infective endocarditis (IE) is rare, and involvement of two valves is rarer yet. We present a case of a 22-year-old male with liver failure who was found to have bivalvular IE. This case sheds light on the association between bivalvular IE and seemingly unrelated symptoms, emphasizing the need for early recognition.

Impella Versus Extracorporeal Membranous Oxygenation (ECMO) for Cardiogenic Shock: A Systematic Review and Meta-analysis.

The use of mechanical circulatory support (MCS) in cardiogenic shock (CS) is increasing. We conducted a systematic review and meta-analysis to compare the outcomes of Impella use with extracorporeal membranous oxygenation (ECMO) support in patients with CS. We searched the Medline, EMBASE, Cochrane, and Clinicaltrials.gov databases for observational studies comparing Impella to ECMO in patients with CS. Risk ratios (RRs) for categorical variables and standardized mean differences (SMDs) for continuous variables were calculated with 95% confidence intervals (CIs) using a random-effects model. Twelve retrospective studies and one prospective study (Impella n=6652, ECMO n=1232) were identified. Impella use was associated with lower incidence of in-hospital mortality (RR 0.88 [95% CI 0.80-0.94], P=0.0004), stroke (RR 0.30 [0.21-0.42], P<0.00001), access-site bleeding (RR 0.50 [0.37-0.69], P<0.0001), major bleeding (RR 0.56 [0.39-0.80], P=0.002), and limb ischemia (RR 0.42 [0.27-0.65], P=0.0001). Baseline lactate levels were significantly lower in the Impella group (SMD -0.52 [-0.73- -0.31], P<0.00001). There was no significant difference in mortality at 6-12 months, MCS duration, need for MCS escalation, bridge-to-LVAD or heart transplant, and renal replacement therapy use between Impella and ECMO groups. In patients with CS, Impella device use was associated with lower in-hospital mortality, stroke, and device-related complications than ECMO. However, patients in the ECMO group had higher baseline lactate levels.

Suppression of Inflammatory Cardiac Cytokine Network in Rats with Untreated Obesity and Pre-Diabetes by AT2 Receptor Agonist NP-6A4.

Obesity affects over 42% of the United States population and exacerbates heart disease, the leading cause of death in men and women. Obesity also increases pro-inflammatory cytokines that cause chronic tissue damage to vital organs. The standard-of-care does not sufficiently attenuate these inflammatory sequelae. Angiotensin II receptor AT2R is an anti-inflammatory and cardiovascular protective molecule; however, AT2R agonists are not used in the clinic to treat heart disease. NP-6A4 is a new AT2R peptide agonist with an FDA orphan drug designation for pediatric cardiomyopathy. NP-6A4 increases AT2R expression (mRNA and protein) and nitric oxide generation in human cardiovascular cells. AT2R-antagonist PD123319 and AT2RSiRNA suppress NP-6A4-effects indicating that NP-6A4 acts through AT2R. To determine whether NP-6A4 would mitigate cardiac damage from chronic inflammation induced by untreated obesity, we investigated the effects of 2-weeks NP-6A4 treatment (1.8 mg/kg delivered subcutaneously) on cardiac pathology of male Zucker obese (ZO) rats that display obesity, pre-diabetes and cardiac dysfunction. NP-6A4 attenuated cardiac diastolic and systolic dysfunction, cardiac fibrosis and cardiomyocyte hypertrophy, but increased myocardial capillary density. NP-6A4 treatment suppressed tubulointerstitial injury marker urinary ß-NAG, and liver injury marker alkaline phosphatase in serum. These protective effects of NP-6A4 occurred in the presence of obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia, and without modulating blood pressure. NP-6A4 increased expression of AT2R (consistent with human cells) and cardioprotective erythropoietin (EPO) and Notch1 in ZO rat heart, but suppressed nineteen inflammatory cytokines. Cardiac miRNA profiling and in silico analysis showed that NP-6A4 activated a unique miRNA network that may regulate expression of AT2R, EPO, Notch1 and inflammatory cytokines, and mitigate cardiac pathology. Seventeen pro-inflammatory and pro-fibrotic cytokines that increase during lethal cytokine storms caused by infections such as COVID-19 were among the cytokines suppressed by NP-6A4 treatment in ZO rat heart. Thus, NP-6A4 activates a novel anti-inflammatory network comprised of 21 proteins in the heart that was not reported previously. Since NP-6A4's unique mode of action suppresses pro-inflammatory cytokine network and attenuates myocardial damage, it can be an ideal adjuvant drug with other anti-glycemic, anti-hypertensive, standard-of-care drugs to protect the heart tissues from pro-inflammatory and pro-fibrotic cytokine attack induced by obesity.

Sipuleucel-T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database.

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.

Cardiovascular disease progression in female Zucker Diabetic Fatty rats occurs via unique mechanisms compared to males.

Population studies have shown that compared to diabetic men, diabetic women are at a higher risk of cardiovascular disease. However, the mechanisms underlying this gender disparity are unclear. Our studies in young murine models of type 2 diabetes mellitus (T2DM) and cardiovascular disease show that diabetic male rats develop increased cardiac fibrosis and suppression of intracardiac anti-fibrotic cytokines, while premenopausal diabetic female rats do not. This protection from cardiac fibrosis in female rats can be an estrogen-related effect. However, diabetic female rats develop early subclinical myocardial deformation, cardiac hypertrophy via elevated expression of pro-hypertrophic miR-208a, myocardial damage, and suppression of cardio-reparative Angiotensin II receptor 2 (Agtr2). Diabetic rats of both sexes exhibit a reduction in cardiac capillary density. However, diabetic female rats have reduced expression of neuropilin 1 that attenuates cardiomyopathy compared to diabetic male rats. A combination of cardiac hypertrophy and reduced capillary density likely contributed to increased myocardial structural damage in diabetic female rats. We propose expansion of existing cardiac assessments in diabetic female patients to detect myocardial deformation, cardiac hypertrophy and capillary density via non-invasive imaging, as well as suggest miR-208a, AT2R and neuropilin 1 as potential therapeutic targets and mechanistic biomarkers for cardiac disease in females.

Systematic review of non-invasive cardiovascular imaging in the diagnosis of constrictive pericarditis.

BACKGROUND: Diagnosis of constrictive pericarditis (CP) can be challenging. It can be nearly impossible to distinguish CP from other causes of right heart failure. Although various imaging modalities help in the diagnosis, no test is definitive. Several reviews have addressed the role of various imaging techniques in the diagnosis of CP but a systematic review has not yet been published. OBJECTIVE: Our intention was to study the ability of various non-invasive imaging modalities to diagnose CP in patients with surgically confirmed disease and to apply our findings to develop a clinically useful diagnostic algorithm. METHODS: A PubMed (NLM) search was performed with MeSH term "constrictive pericarditis". Original articles that investigated the ability of various cardiovascular imaging modalities to noninvasively diagnose surgically confirmed CP were included in our review. Investigations that included any cases without surgical confirmation were excluded. RESULTS: The PubMed search yielded 3001 results with MeSH term "constrictive pericarditis" (January 8, 2016). We identified (40) studies on CP that matched our inclusion criteria. We summarized our results sorted by individual non-invasive CV imaging modalities - echocardiography, cardiac computed tomography (CT), and magnetic resonance imaging (MRI). Under each imaging modality, we grouped our discussion based on different parameters useful in CP diagnosis. CONCLUSIONS: In conclusion, contemporary diagnosis of CP is based on clinical features and echocardiography. Cardiac MRI is recommended in patients where echocardiography is not diagnostic. Both cardiac MRI and CT can guide surgical planning but we prefer MRI as it provides both structural and functional information.

Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension.

The mineralocorticoid aldosterone is a key hormone in the regulation of plasma volume and blood pressure in man. Excessive levels of this mineralocorticoid have been shown to mediate metabolic disorders and end-organ damage more than what can be attributed to its effects on blood pressure alone. Inappropriate excess levels of aldosterone contribute significantly to the cardiorenal metabolic syndrome and target organ injury that include atherosclerosis, myocardial hypertrophy, fibrosis, heart failure, and kidney disease. The importance of understanding the role of excess mineralocorticoid hormones such as aldosterone in resistant hypertension and in those with secondary hypertension should be visited. Primary aldosteronism is one of the commonly identified causes of hypertension and is treatable and/or potentially curable. We intend to review the management of mineralocorticoid-induced hypertension in the adult population along with other disease entities that mimic primary aldosteronism.

Effect of weight loss on ventricular repolarization in normotensive severely obese patients with and without heart failure.

BACKGROUND: Obesity has been reported to be associated with delayed ventricular repolarization. The purpose of this study was to assess ventricular repolarization in normotensive severely obese subjects with and without heart failure (HF) and to assess the effect of weight loss on ventricular repolarization in such patients. METHODS: Twenty-eight patients with and 39 patients without HF (body mass index ≥ 40 kg/m(2)) were studied before and after weight loss from bariatric surgery. Corrected QT interval (QTc) was measured on 12-lead electrocardiograms using Bazett's formula. QTc dispersion was calculated by subtracting the minimum from the maximum QTc on each 12-lead electrocardiogram. Electrocardiograms and transthoracic echocardiograms were performed preoperatively and at the nadir of postoperative weight loss. RESULTS: Mean QTc and QTc dispersion were significantly longer/greater in subjects with HF than in those without HF (P < 0.0001). Weight loss produced significant reductions in mean QTc and QTc dispersion in both subgroups (P < 0.0001). Pre-weight loss left ventricular (LV) mass/height and presence or absence of HF independently predicted pre-weight loss QTc and QTc dispersion (P < 0.0001). Weight loss-induced decrease in LV mass/height independently predicted weight loss-induced decreases in QTc and QTc dispersion (P < 0.0001). CONCLUSIONS: HF independently predicts QTc and QTc dispersion in normotensive severely obese patients. Decrease in the LV mass resulting from weight loss independently predicts reduction in QTc and QTc dispersion in such patients.

Cardiovascular disease in chronic kidney disease: risk factors, pathogenesis, and prevention.

Patients with chronic kidney disease (CKD) experience serious adverse cardiovascular (CV) consequences. Cardiovascular disease is the leading cause of morbidity and mortality in patients with CKD, being secondary not only to an increased prevalence of traditional CV risk factors, but also to the presence of a wide array of nontraditional risk factors unique to patients with CKD. Pathogenesis includes both functional and structural alterations in the CV system. Those alterations give rise to a wide range of clinical CV syndromes, including ischemic heart disease, heart failure, and sudden cardiac arrest. As an increasingly prevalent disease, CKD, together with consequent CV disease, imparts major health and economic burdens to the community. In this review, we discuss traditional and nontraditional risk factors for CV disease, the pathogenesis of CV clinical syndromes, and prevention of CV syndromes in patients with CKD.

Cardiac stimulation with electronic control device application.

BACKGROUND: Electronic control devices (ECDs) are weapons used to incapacitate violent subjects. Subjects have died suddenly after ECD application, but because cardiac dysrhythmias have been inconsistently observed during ECD application in animals, the cause for death is uncertain. OBJECTIVES: The objective was to identify the factors contributing to cardiac stimulation during ECD application detected by transesophageal echocardiography. METHODS: Four Yorkshire pigs were anesthetized, paralyzed with vecuronium, and restrained in a supine position. A GE 6T echo probe was placed in the esophagus to directly visualize left ventricular function. M-mode echocardiography was used to estimate heart rate. Two dart locations, chest and abdomen, were assessed. ECD applications were delivered from one of five commercially available devices (Taser X26, Singer S200 AT, Taser M26, Taser X3, and Taser C2) in random order to each pig, four times in each orientation. RESULTS: Cardiac stimulation, characterized by multiple PVCs or the sudden increase in ventricular contraction rate during application, did not occur with abdominal dart location. With chest dart application in small pigs, cardiac stimulation occurred with all ECDs except with the Taser X3 (p < 0.0001). In large pigs, cardiac stimulation occurred only during chest application of the S200 AT (chest vs. abdomen: 207 beats/min, vs. 91 beats/min, p < 0.0001). CONCLUSION: Cardiac stimulation occurs during ECD application in pigs, and is dependent upon subject size, dart orientation, and ECD. The Taser X3 did not result in cardiac stimulation in small or large pigs.

Impact of obesity and weight loss on cardiac performance and morphology in adults.

Obesity, particularly severe obesity is capable of producing hemodynamic alterations that predispose to changes in cardiac morphology and ventricular function. These include increased cardiac output, left ventricular hypertrophy and diastolic and systolic dysfunction of both ventricles. Facilitated by co-morbidities such as hypertension, the sleep apnea/obesity hypoventilation syndrome, and possibly certain neurohormonal and metabolic alterations, these abnormalities may predispose to left and right heart failure, a disorder known as obesity cardiomyopathy.

Renin inhibition and AT(1)R blockade improve metabolic signaling, oxidant stress and myocardial tissue remodeling.

OBJECTIVE: Strategies that block angiotensin II actions on its angiotensin type 1 receptor or inhibit actions of aldosterone have been shown to reduce myocardial hypertrophy and interstitial fibrosis in states of insulin resistance. Thereby, we sought to determine if combination of direct renin inhibition with angiotensin type 1 receptor blockade in vivo, through greater reductions in systolic blood pressure (SBP) and aldosterone would attenuate left ventricular hypertrophy and interstitial fibrosis to a greater extent than either intervention alone. MATERIALS/METHODS: We utilized the transgenic Ren2 rat which manifests increased tissue expression of murine renin which, in turn, results in increased renin-angiotensin system activity, aldosterone secretion and insulin resistance. Ren2 rats were treated with aliskiren, valsartan, the combination (aliskiren+valsartan), or vehicle for 21 days. RESULTS: Compared to Sprague-Dawley controls, Ren2 rats displayed increased systolic blood pressure, elevated serum aldosterone levels, cardiac tissue hypertrophy, interstitial fibrosis and ultrastructural remodeling. These biochemical and functional alterations were accompanied by increases in the NADPH oxidase subunit Nox2 and 3-nitrotyrosine content along with increases in mammalian target of rapamycin and reductions in protein kinase B phosphorylation. Combination therapy contributed to greater reductions in systolic blood pressure and serum aldosterone but did not result in greater improvement in metabolic signaling or markers of oxidative stress, fibrosis or hypertrophy beyond either intervention alone. CONCLUSIONS: Thereby, our data suggest that the greater impact of combination therapy on reductions in aldosterone does not translate into greater reductions in myocardial fibrosis or hypertrophy in this transgenic model of tissue renin overexpression.

Statins reduce appropriate implantable cardioverter-defibrillator shocks in ischemic cardiomyopathy with no benefit in nonischemic cardiomyopathy.

Statins have been hypothesized to decrease ventricular arrhythmias through a direct antiarrhythmic effect. Clinical studies have demonstrated a clear reduction only in populations with underlying ischemic heart disease. This study was designed to compare the effect of statins on appropriate shocks between ischemic and nonischemic cardiomyopathy. Patients with an ejection fraction 35% or less who received an implantable cardioverter-defibrillator and had follow-up for at least 1 month were included. The ischemic and nonischemic groups were divided into statin treatment and control subgroups and the occurrence of appropriate shocks was compared. The frequency of shocks was analyzed using negative binomial models to account for overdispersion of the "count" data (number of appropriate shocks) and an adjusted intensity rate ratio was calculated for statin use. A total of 676 patients were included, of which statins were used by 65% (329 of 506) of the ischemic and 42% (72 of 170) of the nonischemic groups. Occurrence of appropriate shocks was significantly reduced with statins in ischemic (13.4% vs 20.9%; relative risk 0.64, P = 0.028), but not in the patients with nonischemic cardiomyopathy. Similarly, although use of statins lowered the intensity rate of appropriate shocks in ischemic patients (intensity rate ratio, 0.23; 95% confidence interval, 0.12-0.47), no such benefit was noted in the nonischemic group (intensity rate ratio, 1.27; 95% confidence interval, 0.37-4.40). In conclusion, statins reduced the occurrence and frequency of appropriate shocks for ventricular arrhythmias in ischemic but not in nonischemic cardiomyopathy. Larger, randomized controlled trials are needed to confirm these findings.

Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities.

In conditions of overnutrition, cardiac cells must cope with a multitude of extracellular signals generated by changes in nutrient load (glucose, amino acids, and lipids) and the hormonal milieu [increased insulin (INS), ANG II, and adverse cytokine/adipokine profile]. Herein, we review the diverse compensatory/adaptive mechanisms that counter the deleterious effects of excess nutrients and growth factors. We largely focus the discussion on evidence obtained from Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats, which are useful models to evaluate adaptive and maladaptive metabolic, structural, and functional cardiac remodeling. One adaptive mechanism present in the INS-resistant ZO, but absent in the diabetic ZDF heart, involves an interaction between the nutrient sensor kinase mammalian target of rapamycin complex 1 (mTORC1) and ANG II-type 2 receptor (AT2R). Recent evidence supports a cardioprotective role for the AT2R; for example, suppression of AT2R activation interferes with antihypertrophic/antifibrotic effects of AT1R blockade, and AT2R agonism improves cardiac structure and function. We propose a scenario, whereby mTORC1-signaling-mediated increase in AT2R expression in the INS-resistant ZO heart is a cardioprotective adaptation to overnutrition. In contrast to the ZO rat, heart tissues of ZDF rats do not show activation of mTORC1. We posit that such a lack of activation of the mTOR↔AT2R integrative pathway in cardiac tissue under conditions of obesity-induced diabetes may be a metabolic switch associated with INS deficiency and clinical diabetes.

Reduction in the intensity rate of appropriate shocks for ventricular arrhythmias with statin therapy.

Higher rate of implantable cardioverter-defibrillator (ICD) shocks has been associated with increased mortality and morbidity. The aim of our study was to determine whether statins reduced the intensity rate of appropriate shock therapy for ventricular tachycardia/fibrillation in patients with an ICD placed for left ventricular systolic dysfunction. In this retrospective single center analysis, patients with an ejection fraction

Myocardial infarction--fusion or confusion?

A patient with a dualchamber pacemaker with dynamic atrioventricular delay (AVD) experienced acute substernal chest pain. The rhythm strip in the ambulance showed intermittent ST elevation in the inferior leads. An emergent cardiac catheterization revealed nonobstructive coronary artery disease. Rate-responsive dual-chamber pacing with dynamic AVD was responsible for varying devvgrees of ventricular fusion due to competition with the patient's normal conduction. Intermittent ST elevation, evident only during ventricular fusion should have suggested secondary ventricular repolarization and not myocardial injury, but concomitant chest pain and inconspicuous bipolar pacing artifacts added to the confusion. Ventricular pacing may not only mask acute ST-T changes due to myocardial injury, but can also mimic acute myocardial infarction.

Inappropriate Implantable Cardioverter-Defibrillator Therapy.

Although improvements in implantable cardioverter-defibrillator (ICD) therapy have taken place, many challenges do remain. Inappropriate delivery of therapy is a big problem that impacts the quality of life of ICD recipients. Although there is now a clear understanding that atrial arrhythmias are the main cause of inappropriate ICD therapies, physicians have not been very successful in preventing them. Additionally, although many tachycardia detection discriminators have been shown to be helpful, it is not clear that there is a particular combination that is ideal for all patients. Until such an algorithm is developed (which may not be possible), a detailed knowledge and use of all available programming options, guided by special characteristics of each unique patient, are the only foreseeable solutions. Finally, one must face the prospect that this problem cannot be vanquished, but only ameliorated.

Brainstem infarct presenting as torsades de pointes.

Hypokalemia, as an adverse consequence of severe alkalosis, can prolong QT interval and cause torsades de pointes. This report describes a rare case of central neurogenic hyperventilation as a result of brainstem infarct, presenting primarily with refractory ventricular tachyarrhythmia due to secondary hypokalemia.

HIV Myocarditis Presenting as Acute ST-Segment Elevation Myocardial Infarction.

Myocarditis is a common occurrence among patients infected with human immunodeficiency virus (HIV). However, it is rare to find HIV-associated myocarditis presenting as ST-segment elevation myocardial infarction with cardiogenic shock. A case of HIV-related myocarditis presenting as an acute inferolateral wall myocardial infarction in a 32-year-old male is described.