Markers of responsiveness to disopyramide in patients with hypertrophic cardiomyopathy.

BACKGROUND: Significant left-ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients, nearly 30% of HCM patients do not respond. We sought to study the clinical and echocardiographic variables associated with disopyramide-induced LVOT-gradient reduction. METHODS: Forty-one disopyramide-treated HCM patients (average daily-dose 305 mg) were subdivided into two groups: (1) nineteen responders, with a reduction of LVOT-gradients of at least 30% from baseline, and (2) twenty-two non-responders, in whom LVOT-gradients did not change or increased following treatment. All patients had a thorough clinical and echocardiographic assessment pre- and post-treatment initiation. RESULTS: Patients who responded to disopyramide had better pretreatment left ventricular (LV) systolic function (LV ejection fraction of 67.9 ±â€¯5.6% vs. 59.7 ±â€¯5.8%, p = 0.0001), better LV global longitudinal strain (-17.9 ±â€¯2.3% vs. -16.1 ±â€¯2.5%, p = 0.048), less mitral regurgitation, smaller LV size (indexed LV end-systolic volume of 16.2 ±â€¯5.1 ml/m2 vs. 23.2 ±â€¯6.8 ml/m2, p = 0.001), and lower LV maximal wall thickness (17.2±3 mm vs.19.2 ±â€¯3.4 mm, p = 0.046). Baseline left atrial (LA) volumes were significantly lower in the responders, with higher indices of LA ejection fraction (62 ±â€¯11.2% vs. 50.5 ±â€¯12.2%, p = 0.005), systolic LA strain (34 ±â€¯12.4% vs. 25.8 ±â€¯10.6%, p = 0.04), and LA strain-rate (1.34 ±â€¯0.49%/sec vs. 0.99 ±â€¯0.24%/sec, p = 0.012). In multivariable analysis, the presence of reduced LV systolic function and systolic LA strain-rate remained independently associated with poor response to disopyramide. CONCLUSIONS: Obstructive HCM patients with more severe disease at baseline tend to respond less to disopyramide treatment. In those patients, early referral for alcohol septal ablation or myectomy surgery should be considered.

Takotsubo Cardiomyopathy in a Patient with Previously Undiagnosed Hypertrophic Cardiomyopathy with Latent Obstruction.

A 62-year-old woman with takotsubo cardiomyopathy (TCM) accompanied by cardiogenic shock due to the obstruction of left ventricular outflow tract (LVOT) and massive mitral regurgitation (MR) was admitted to the emergency department. After successful treatment with intensive care, dobutamine stress-echocardiography was performed, which reproduced a dynamic LVOT gradient, severe MR and cardiogenic shock. A histological examination obtained from the right ventricular septum demonstrated hypertrophied and bizarre myocytes, with myocyte disarray. Besides TCM, a diagnosis of preexisting hypertrophic cardiomyopathy with latent obstruction was made. She was discharged with medical therapy including a beta-blocker, which would not be routinely employed in the treatment of a patient with TCM.

Successful negative inotropic treatment of acute left ventricular outflow tract obstruction by elongated mitral valve leaflet.

Elongated anterior mitral valve leaflet (EAMVL) has not been reported to cause left ventricular outflow tract obstruction (LVOTO) in the absence of left ventricular hypertrophy. We report the case of an elderly male patient who presented with acute heart failure and severe mitral regurgitation in the setting of dehydration. Echocardiography revealed acute LVOTO secondary to EAMVL. The patient was ineligible for surgery and was treated with negative inotropic agents, which ensured resolution of heart failure and marked improvement in the degree of LVOTO. This case demonstrates that, under certain circumstances, EAMVL without associated left ventricular hypertrophy may produce hemodynamic compromise that can be successfully treated medically.

Left ventricular outflow tract occluding thrombus after biventricular mechanical circulatory support as a bridge to recovery.

The role of mechanical circulatory support for cardiopulmonary failure is expanding. Anticoagulation in the setting of static blood, hypercoagulable states, extracorporeal circuits, and surgery presents an intricate and delicate balance. We present a patient with large, biventricular thrombi during and succeeding biventricular mechanical support. Management of the thrombi and device selection in this patient are discussed.

Successful treatment of neonatal pulmonary thrombosis in congenital nephrotic syndrome.

A 21-year-old adult patient with Tetralogy of Fallot presented acutely unwell with a 3-month history of general malaise following dental treatment. Following initial complete repair, he subsequently underwent two right ventricular outflow tract reconstructions with conduits. On admission, transthoracic echocardiography and peripheral blood cultures were suggestive of streptococcal endocarditis. Sequential computed tomography pulmonary angiography demonstrated peripheral emboli with progressive central pulmonary artery filling defects suggestive of thrombi and potential vegetations (Fig 1a and b). Urgent surgery was performed for uncontrolled sepsis and increasing hypoxia. Peri-operative transesophageal echocardiogram confirmed previous findings (Fig 1c; Supplementary Video 1). Having resected the conduit, we performed a peripheral pulmonary embolectomy and resected an abundance of the infected material from the pulmonary arterial tree under low-flow hypothermia; we then proceeded with a jugular venous valved conduit (Contegra®, Medtronic Inc, Minneapolis, Minnesota, United States of America) replacement and tricuspid valve annuloplasty. He made a slow but steady recovery and was discharged home in good health

[Mitral valve dysplasia in a cat causing reversible left ventricular hypertrophy and dynamic outflow tract obstruction]. / Mitraalklepdysplasie als oorzaak voor een reversibele hypertrofie en dynamische uitstroombaanobstructie van de linker ventrikel bij een kat.

A 6-month-old male European shorthair cat was examined because of a 2/6 systolic left apical cardiac murmur. Echocardiography revealed severe concentric left ventricular hypertrophy and severe dynamic left ventricular outflow tract obstruction (pressure gradient of 85 mmHg) caused by systolic anterior motion (SAM) of the septal mitral valve leaflet. After 2 months of oral treatment with atenolol, the cardiac murmur had disappeared. Echocardiography showed only slight thickening of the interventricular septum and resolution of the pressure gradient. The cat was discharged and its owner was advised to continue atenolol lifelong. Echocardiographic findings of a combination of left ventricular concentric hypertrophy and dynamic left ventricular outflow tract obstruction can be caused by hypertrophic obstructive cardiomyopathy (HOCM) or mitral valve dysplasia in the absence of hypertension and fixed aortic stenosis. In the case of HOCM, left ventricular hypertrophy is the primary process. In the case of mitral valve dysplasia, systolic anterior motion of the mitral valve is the primary problem, which leads to dynamic left ventricular outflow tract obstruction and ultimately to left ventricular concentric hypertrophy, due to pressure overload. If the left ventricular outflow tract obstruction is reduced with an oral beta-receptor blocker the secondary left ventricular hypertrophy may resolve. This would not happen in the case of hypertrophic obstructive cardiomyopathy. To the best of the authors' knowledge, this is the first documented case of severe dynamic left ventricular outflow tract obstruction and severe left ventricular hypertrophy in a cat successfully treated with oral atenolol.

The clinical implications of isolated alpha(1) adrenergic stimulation.

Phenylephrine is a direct-acting, predominantly α(1) adrenergic receptor agonist used by anesthesiologists and intensivists to treat hypotension. A variety of physiologic studies suggest that α-agonists increase cardiac afterload, reduce venous compliance, and reduce renal bloodflow. The effects on gastrointestinal and cerebral perfusion are controversial. To better understand the effects of phenylephrine in a variety of clinical settings, we screened 463 articles on the basis of PubMed searches of "methoxamine," a long-acting α agonist, and "phenylephrine" (limited to human, randomized studies published in English), as well as citations found therein. Relevant articles, as well as those discovered in the peer-review process, were incorporated into this review. Phenylephrine has been studied as an antihypotensive drug in patients with severe aortic stenosis, as a treatment for decompensated tetralogy of Fallot and hypoxemia during 1-lung ventilation, as well as for the treatment of septic shock, traumatic brain injury, vasospasm status-postsubarachnoid hemorrhage, and hypotension during cesarean delivery. In specific instances (critical aortic stenosis, tetralogy of Fallot, hypotension during cesarean delivery) in which the regional effects of phenylephrine (e.g., decreased heart rate, favorable alterations in Q(p):Q(s) ratio, improved fetal oxygen supply:demand ratio) outweigh its global effects (e.g., decreased cardiac output), phenylephrine may be a rational pharmacologic choice. In pathophysiologic states in which no regional advantages are gained by using an α(1) agonist, alternative vasopressors should be sought.

Endogenous catecholamine levels and function of the systemic right ventricle following atrial switch.

BACKGROUND: As a result of successful surgery there is a large cohort of young adults with systemic right ventricles, suffering from progressive right ventricular dysfunction. Beta-blockers are successfully used in left ventricular failure. We assessed catecholamine levels and related it to cardiac function late following atrial switch, to provide the pathophysiologic basis for pharmacotherapy in patients with systemic right ventricles. METHODS: It was a prospective study of 23 consecutive adult patients with the complete transposition of the great arteries, following atrial switch. Epinephrine and norepinephrine concentrations were measured with high performance liquid chromatography. RESULTS: Mean+/-SD epinephrine and norepinephrine levels were 54.5+/-29.0 pg/mL and 389.6+/-134.2 pg/mL, respectively. In multivariate stepwise regression models, sex (B=-0.455, 95% CI for B of -0.887 to -0.023, P=0.04), age (B=-1.328, 95% CI for B of -2.402 to -0.254, P=0.018), and cardiothoracic ratio (B=2.302, 95% CI for B of 0.120-4.484, P=0.04) were significant predictors of epinephrine levels. Diastolic right ventricular cavity area (B=0.024, 95% CI for B of 0.009-0.038, P=0.003) was a significant predictor of norepinephrine levels. Significantly higher levels of epinephrine were observed in patients with vs without left ventricular tract obstruction (88.0+/-15.5 vs 47.4+/-26.2 pg/mL, P=0.008). CONCLUSIONS: We have demonstrated a significant correlation between right ventricular enlargement and epinephrine as well as norepinephrine levels. Elevated catecholamine levels were observed in patients with left ventricular tract obstruction. This supports the use of beta-blockers in the selected patients with systemic right ventricles following atrial switch.

Churg-strauss syndrome presenting with cardiac mass and right ventricular obstruction.

A 57-year-old woman presenting with asthma, hypereosinophilia, and generalized unspecific symptoms was diagnosed with Churg-Strauss syndrome. Echocardiography revealed a cardiac mass obliterating the right ventricle and severely impaired left ventricular function, which were caused by endomyocardial fibrosis. Cortisone and cyclophosphamide therapy resulted in amelioration of left ventricular function and significant size reduction of the right ventricular mass.

Cibenzoline improves coronary flow velocity reserve in patients with hypertrophic obstructive cardiomyopathy.

The effect of cibenzoline, a class-Ia antiarrhythmic drug, on coronary flow velocity reserve (CFVR) was examined in patients with hypertrophic cardiomyopathy using transthoracic Doppler echocardiography. Coronary flow velocity reserve was assessed in 11 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 12 patients with hypertrophic nonobstructive cardiomyopathy (HNCM), before and after the intravenous administration of cibenzoline (1 mg/kg). Coronary hyperemia was induced by an intravenous infusion of adenosine triphosphate and CFVR was calculated as the ratio of hyperemic to basal mean coronary diastolic flow velocity. At baseline, CFVR was significantly correlated with left ventricular outflow tract pressure gradient (LVPG) in patients with HOCM (r = 0.67, P < 0.03). In patients with HOCM, administration of cibenzoline significantly improved impaired CFVR (2.0 +/- 0.8 to 3.0 +/- 1.0, P < 0.001), and reduced LVPG (55 +/- 30 to 23 +/- 18 mmHg, P < 0.001), while CFVR remained unchanged in patients with HNCM (2.6 +/- 0.9 to 2.9 +/- 0.8, P not significant). Cibenzoline not only reduces LVPG but also improves CFVR in patients with HOCM. In addition left ventricular outflow obstruction plays an important role in impaired coronary circulation in patients with HOCM.

Relief of left ventricular outflow obstruction by cibenzoline in a patient with Fabry's disease--a case report.

A 46-year-old man was admitted for further evaluation of exertional chest discomfort. One family member had experienced sudden death, and 2 others had died of heart failure, including 1 known to have had Fabry's disease. The patient was also diagnosed with Fabry's disease, based on reduced leukocyte alpha-galactosidase A activity, 2.0 nmol/mg protein/hour, as well as endomyocardial biopsy findings of marked sarcoplasmic vacuolization of cardiac muscle cells by light microscopy and lamellated "zebra bodies'' in the cytoplasm shown by electron microscopy. Echocardiography disclosed marked left ventricular hypertrophy and systolic anterior motion of the mitral leaflets. On cardiac catheterization, a left ventricular peak systolic outflow gradient of 50 mm Hg was noted; this decreased to 10 mm Hg following intravenous administration of 100 mg of cibenzoline. It is imperative to recognize the existence of cases with Fabry's disease associated with left ventricular outflow obstruction.

Theories on the nature of the coupling between ventilation and gas exchange during exercise.

For over a century of creative research, many theories on the possible mechanisms controlling respiration during exercise have been developed and discussed. One of the most enduring questions is certainly related to the mechanisms that can prevent P(a)(CO(2)) rising when CO(2) production increases. As multiple systems and structures are capable of increasing ventilation (V (E)), not all the mechanisms controlling respiration can provide a proper answer to this question. Indeed, exercise is a complex physiological condition combining motor activity with a change in metabolic rate. The most intriguing aspect of exercise is that when the changes in metabolism are dissociated from the motor and locomotor activity, the strategy 'chosen' by the respiratory control system is to follow the metabolic rate (or more precisely factors temporally associated with the pulmonary gas exchange rate) regardless of the motor act. The strategy used by the respiratory system during exercise therefore appears to select from among various sources of information the most relevant to follow the rate at which CO(2) is ultimately exchanged by the lungs. Yet, the nature of the signal(s) which prevents CO(2)/H(+) disturbance during exercise is the fundamental question addressed by this simple observation and remains to be clarified. This review illustrates the attempts of many physiologists to collect experimental evidence for theories which could provide satisfactory mechanisms accounting for the matching between ventilation and the rate at which CO(2) leaves the tissues and is exchanged at the lungs. More recent models based on somatic information of circulatory origin are presented and discussed.

Right ventricular metastatic choriocarcinoma obstructing inflow and outflow tract.

We operated on a 34-year-old man with a metastatic tumor that extended from the tricuspid valve to the pulmonary valve and obstructed the right ventricle inflow and outflow tracts. The tumor was removed with preservation of the tricuspid valve. Additional chemotherapy was carried out according to the BEPO (etoposid, eisplatin, bleomycin, vincritin) scheme. Histology revealed metastasis of a choriocarcinoma originating from the right testis. Computed tomography performed after 6 months detected no metastases in the lungs. Magnetic resonance imaging showed a thickened right ventricle free wall and apex. The patient is doing well 18 months postoperatively.

Obstruction of the left ventricular outflow tract after mitral valvuloplasty with implantation of Gregori's ring.

Mitral valvuloplasty is efficient for repairing mitral valve disease with few complications. In some cases, obstruction of the left ventricular outflow tract may occur due to systolic anterior motion of the mitral valve. We report the case of a patient with this complication and a pressure gradient between the left ventricle and the aorta of 130 mm Hg after mitral valvuloplasty with implantation of a Gregori's ring. The management was clinical with suspension of the vasoactive drugs and introduction of a beta-blocker. Two years after the surgery, the patient is asymptomatic and has a normal life.

An intraoperative diagnosis of dynamic left ventricular outflow tract obstruction using transesophageal echocardiography leads to the treatment with intravenous disopyramide.

UNLABELLED: Hypertrophic obstructive cardiomyopathy (HOCM) is an uncommon familial disorder, traditionally characterized by asymmetric septal hypertrophy and left ventricular outflow tract (LVOT) obstruction (1). It is now recognized that HOCM may also include those patients with secondary left ventricular hypertrophy (LVH) and dynamic LVOT obstruction. In particular, a syndrome with similar clinical and echocardiographic findings has been identified in elderly patients exhibiting concentric LVH with chronic hypertension, aortic stenosis, or sigmoid-shaped septum (2). IMPLICATIONS: During surgery, dynamic left ventricular outflow obstruction (LVOT) can potentially occur frequently, but diagnosis may be less frequent. When circulatory disturbance occurs with suspicion of LVOT obstruction, transesophageal echocardiography can provide exact proof of diagnosis and basis for immediate treatment.

Cardiac extension of primary mediastinal seminoma compressing the right ventricular outflow tract.

We report the case of a 33-year-old male with primary seminoma of the anterior mediastinum with initial clinical manifestations suggestive of heart disease.

Extensäo cardíaca de seminoma primário do mediastino, comprimindo a via do ventrículo direito / Cardiac extension of primary mediastinal seminoma compressing the right ventricular outflow tract

We report the case of a 33-year-old male with primary seminoma of the anterior mediastinum with initial clinical manifestations suggestive of heart disease