Norepinephrine-associated left ventricular outflow tract obstruction and systolic anterior movement.

In the perioperative setting, norepinephrine is used to increase blood pressure, an effect mediated mostly via arterial and venous vasoconstriction. Thus, norepinephrine is, allegedly, less likely to cause or worsen left ventricular outflow tract obstruction (LVOTO) than other inotropes. We report a case of norepinephrine-associated dynamic LVOTO and systolic anterior movement in a predisposed patient. This report highlights that unrecognised dynamic LVOTO may worsen shock parameters in patients treated with norepinephrine who have underlying myocardial hypertrophy.

Blockade of CaMKII depresses conduction preferentially in the right ventricular outflow tract and promotes ischemic ventricular fibrillation in the rabbit heart.

Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates the principle ion channels mediating cardiac excitability and conduction, but how this regulation translates to the normal and ischemic heart remains unknown. Diverging results on CaMKII regulation of Na+ channels further prevent predicting how CaMKII activity regulates excitability and conduction in the intact heart. To address this deficiency, we tested the effects of the CaMKII blocker KN93 (1 and 2.75 µM) and its inactive analog KN92 (2.75 µM) on conduction and excitability in the left (LV) and right (RV) ventricles of rabbit hearts during normal perfusion and global ischemia. We used optical mapping to determine local conduction delays and the optical action potential (OAP) upstroke velocity (dV/dtmax). At baseline, local conduction delays were similar between RV and LV, whereas the OAP dV/dtmax was lower in RV than in LV. At 2.75 µM, KN93 heterogeneously slowed conduction and reduced dV/dtmax, with the largest effect in the RV outflow tract (RVOT). This effect was further exacerbated by ischemia, leading to recurrent conduction block in the RVOT and early ventricular fibrillation (at 6.7 ± 0.9 vs. 18.2 ± 0.8 min of ischemia in control, P < 0.0001). Neither KN92 nor 1 µM KN93 depressed OAP dV/dtmax or conduction. Rabbit cardiomyocytes isolated from RVOT exhibited a significantly lower dV/dtmax than those isolated from the LV. KN93 (2.75 µM) significantly reduced dV/dtmax in cells from both locations. This led to frequency-dependent intermittent activation failure occurring predominantly in RVOT cells. Thus CaMKII blockade exacerbates intrinsically lower excitability in the RVOT, which is proarrhythmic during ischemia.NEW & NOTEWORTHY We show that calcium/calmodulin-dependent protein kinase II (CaMKII) blockade exacerbates intrinsically lower excitability in the right ventricular outflow tract, which causes highly nonuniform chamber-specific slowing of conduction and facilitates ventricular fibrillation during ischemia. Constitutive CaMKII activity is necessary for uniform and safe ventricular conduction, and CaMKII block is potentially proarrhythmic.

Myocardial infarction induced by oral terazosin in a patient with predisposing structural cardiomyopathy: case report. / Infarto agudo de miocardio asociado al uso de terazosina oral en presencia de cardiopatía estructural predisponente: reporte de caso.

We describe a 71-year-old male patient who developed acute myocardial infarction (AMI) due to a dynamic left ventricular outflow tract obstruction induced by terazosin. After receiving terazosin, the patient had a syncope followed by angina. The electrocardiogram showed Q waves and ST segment elevation in the precordial and inferior leads. Coronary angiography evidenced a chronically occluded left anterior descending artery. Doppler-echocardiography revealed apical akinesia, hyperdynamic basal segments, systolic anterior motion of the mitral valve (SAM) and dynamic left ventricular outflow tract obstruction. Therapy with intravenous fluids and atenolol resulted in marked clinical improvement. Acute myocardial infarction resulted from low coronary perfusion pressure in a patient with a chronically diminished coronary reserve.

Describimos el caso de un hombre de 71 años de edad, que presentó un infarto agudo de miocardio debido a la obstrucción dinámica del tracto de salida del ventrículo izquierdo inducida por la terazosina. Luego de recibir dicha medicación el paciente presentó un síncope y posteriormente angina de pecho. El electrocardiograma evidenció ondas Q y sobreelevación del segmento ST en las derivaciones precordiales e inferiores. La angiografía coronaria evidenció una oclusión crónica de la arteria descendente anterior y el ecocardiograma Doppler reveló aquinesia apical, segmentos basales hiperdinámicos, movimiento anterior sistólico de la válvula mitraI y obstrucción dinámica del tracto de salida del ventrículo izquierdo. La administración intravenosa de suero fisiológico y atenolol determinó una clara mejoría clínica. Un infarto agudo de miocardio hemodinámico fue el resultado de la caída de la presión de perfusión coronaria en un paciente con disminución crónica de la reserva coronaria.

Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy.

PURPOSE: Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. METHODS: We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. RESULTS: Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. CONCLUSION: Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd.

Prednisone induced two-way myocardial development in a patient with systemic lupus erythematosus.

We present a series of echocardiography images to demonstrate the myocardial response to a high dose of prednisone. A young woman with systemic lupus erythematosus (SLE) associated with interventricular septal hypertrophy exhibited a high pressure gradient between the ascending aorta and left ventricular outflow tract as well as significant systolic anterior motion (SAM) and mitral regurgitation (MR) during high-dose prednisone treatment. However, the pressure gradient decreased dramatically and the MR disappeared rapidly when the dose of prednisone was reduced. To the best of our knowledge, this is the only adult case of myocardial hypertrophy that is assumed to be related to prednisone use.

Hypertrophic intraventricular flow obstruction after very-low-dose dexamethasone (Minidex) in preterm infants: case presentation and review of the literature.

The use of dexamethasone in preterm infants developing bronchopulmonary dysplasia has been proven to be effective. Hypertrophic cardiomyopathy is a frequently reported, although transient, side effect of high-dose dexamethasone administration. The recent introduction of very low dexamethasone dose, called 'Minidex', promised equal effectiveness compared to high-dose dexamethasone without relevant side effects. Our study presents two patients developing hypertrophic cardiomyopathy with intraventricular cardiac obstruction after administration of 'Minidex'. Marked cardiac side effects may occur even during very-low-dose dexamethasone treatment in preterm neonates. Betablocker and discontinuation of dexamethasone seem to allow spontaneous reversal of myocardial hypertrophy and obstruction. After all, systematic surveys of the incidence of cardiac complications in a larger population of preterm infants treated with very low doses of dexamethasone are needed.

Lamotrigine-trigged obstructive hypertrophic cardiomyopathy, epilepsy and metabolic myopathy.

Lamotrigine has the advantage to have an antidepressive effect and to be well tolerated in the majority of the cases. Lamotrigine, however, may exert cardiac side effects in patients with hypertrophic cardiomyopathy and latent obstruction of the left ventricular outflow tract, as illustrated by the following case report. In a 67 year-old male with epilepsy, metabolic myopathy and malignant hyperthermia hypertrophic cardiomyopathy was diagnosed by echocardiography. By Doppler-echocardiography the maximal gradient in the left ventricular outflow tract was 57 mm Hg. Because or recurrent seizures, the lamotrigine dosage was increased from 100 mg/d to 200 mg and then to 300 mg/d. After the first intake of 300 mg lamotrigine, the patient felt weak, dizzy and complained about exertional dyspnoea and chest pain. Doppler-echocardiography showed now a maximal gradient of 106 mm Hg in the left ventricular outflow tract. After reducing the lamotrigine dosage to 100 mg/d and adding levetirazetam (1000 mg/d), the patient's condition improved immediately and the outflow-tract-gradient regressed to 12 mm Hg. Cardiac catheterization showed an outflow-tract-gradient of 25-36 mm Hg and normal coronary arteries. From this observation we conclude that care should be taken when prescribing lamotrigine to patients with obstructive hypertrophic cardiomyopathy.

Aggravation of mitral regurgitation by calcium administration in a patient with hypertrophic cardiomyopathy during liver transplantation: a case report.

Aggravation of mitral regurgitation (MR) due to left ventricular outflow tract obstruction (LVOTO) is likely to occur during liver transplantation in cirrhotic patients with hypertrophic cardiomyopathy (HCMP). Moreover, calcium administration following severe hypocalcemia due to inadequate citrate metabolism and massive transfusion may induce MR aggravation with LVOTO in such patients. Herein we have described a cirrhotic patient with HCMP in whom MR was aggravated due to LVOTO resulting from inadvertent rapid administration of calcium during liver transplantation.

Cardiac toxicity with anti-HER-2 therapies: what have we learned so far?

Trastuzumab, a monoclonal antibody that blocks HER-2 receptor, improves the survival of women with HER-2-positive early and advanced breast cancer when given with chemotherapy. Lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2, is approved for the treatment of metastatic breast cancer patients after failure of prior anthracycline, taxanes and trastuzumab therapies in combination with capecitabine. Importantly, cardiac toxicity, manifested as symptomatic congestive heart failure or asymptomatic left ventricular ejection fraction decline, has been reported in some of the patients receiving these novel anti-HER-2 therapies, particularly when these drugs are used following anthracyclines, whose cardiotoxic potential has been recognized for decades. This review will focus on the incidence, natural history, underlying mechanisms, management, and areas of uncertainty regarding trastuzumab-and lapatinib-induced cardiotoxicity.

Dynamic left ventricular outflow tract obstruction without basal septal hypertrophy, caused by catecholamine therapy and volume depletion.

Hypertrophic cardiomyopathy (HCM) with hypertrophy of the basal septum is the most common etiology of left ventricular outflow tract (LVOT) obstruction. In this article, we report the case of a patient with a structurally normal heart who developed hemodynamic deterioration due to severe LVOT obstruction following treatment with catecholamines. Hypovolemia accompanied with a hyperdynamic condition, resulting from catecholamine treatment, may cause dynamic LVOT obstruction due to the systolic anterior motion of the mitral valve leaflet. The solution for this is early recognition and correction of aggravating factors such as, withdrawal of catecholamine therapy and volume replacement.

Cardiac chamber hypertrophy following hematopoietic stem cell transplantation for primary immunodeficiency.

Children with primary immune deficiency (PID) who receive hematopoietic stem cell transplantation (HSCT) often suffer from graft-versus-host disease (GVHD), which is commonly treated with corticosteroids (CS). CS may cause hypertension, development of cardiac chamber hypertrophy (CCH), and left ventricular outflow tract obstruction (LVOTO). We followed the development of CCH and LVOTO by serial echocardiograms in 10 children with PID before and 6 to 12 weeks after HSCT, and correlated their development with age of transplant, GVHD, use of CS and hypertension. CCH developed in all 4 children transplanted before 1 year of age who received high dose CS treatment for grade III or IV acute GVHD (aGVHD), but not in the 6 children who were transplanted at later ages or who had not received high-dose CS (P = .07). Significant correlation (P < .002) was found between CCH and blood pressure measurements that deviated above the 99th percentile. One child also suffered from severe LVOTO. CCH and LVOTO improved when CS treatment was discontinued and blood pressure normalized. We conclude that following HSCT, young children who suffer from aGVHD, treated with high CS doses, and have excessive hypertension are at risk of developing CCH.

Dynamic left ventricular outflow tract obstruction without basal septal hypertrophy, caused by catecholamine therapy and volume depletion

Hypertrophic cardiomyopathy (HCM) with hypertrophy of the basal septum is the most common etiology of left ventricular outflow tract (LVOT) obstruction. In this article, we report the case of a patient with a structurally normal heart who developed hemodynamic deterioration due to severe LVOT obstruction following treatment with catecholamines. Hypovolemia accompanied with a hyperdynamic condition, resulting from catecholamine treatment, may cause dynamic LVOT obstruction due to the systolic anterior motion of the mitral valve leaflet. The solution for this is early recognition and correction of aggravating factors such as, withdrawal of catecholamine therapy and volume replacement.

Dynamic intraventricular obstruction in acute myocardial infarction with administration of cilostazol.

Dynamic intraventricular obstruction is a less well-known mechanical complication of acute myocardial infarction (AMI). Its hallmark is the development of a new systolic murmur, and echocardiography is necessary for diagnosis. We describe a case of a 74-year-old woman with dynamic intraventricular obstruction complicating AMI. Serial echocardiography suggested that the intraventricular gradient was a consequence of basal hyperkinesis, which was a reciprocal response to akinesis of the apical wall. Cilostazol, which was administered to prevent subacute stent thrombosis after percutaneous coronary intervention, might have contributed to the transient intraventricular obstruction.