Impact of septal myectomy on left atrial volume and left ventricular diastolic filling patterns: an echocardiographic study of young patients with obstructive hypertrophic cardiomyopathy.

Background: Septal myectomy in young patients with obstructive hypertrophic cardiomyopathy (HCM) can be performed with low mortality, and leads to excellent improvement in symptoms. Left atrial (LA) enlargement has been associated with exercise intolerance, severity of mitral regurgitation (MR), and left ventricular (LV) outflow tract (LVOT) obstruction in adults with HCM.

Methods: Young patients (1-22 years of age) who had a septal myectomy for obstructive HCM between 2002 and 2005 were identified.

Effects of surgical septal myectomy on left ventricular wall thickness and diastolic filling.

This study was conducted to examine the late effects of surgical myectomy on left ventricular (LV) structure and diastolic function in patients with obstructive hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy who had complete echocardiographic studies before and > or =6 months after myectomy were included in this retrospective analysis of cavity dimension, septal and LV posterior wall thicknesses, and Doppler flow variables. Compared with preoperative measurement, mean septal thickness (23.

Septal myectomy after previous septal artery ablation in hypertrophic cardiomyopathy.

Objective: To review our institution's experience with patients who failed to benefit from septal artery ablation, which necessitated subsequent septal myectomy, and to examine reasons for ablation failure and outcome of myectomy after ablation.

Participants And Methods: Of 550 patients who underwent septal myectomy at Mayo Clinic Rochester between January 1, 1999, and December 31, 2006, 16 (3%) had had a total of 22 previous septal artery ablations. This subset of 16 patients was analyzed and compared with a reference group of 120 patients whose septal artery ablations were performed at our institution during this period.

Evaluation of left ventricular filling pressures by Doppler echocardiography in patients with hypertrophic cardiomyopathy: correlation with direct left atrial pressure measurement at cardiac catheterization.

Background: Diastolic dysfunction is a major pathophysiological abnormality in hypertrophic cardiomyopathy (HCM). Doppler echocardiographic parameters correlate with left ventricular (LV) filling pressures in other diseases, but it is unclear whether these findings apply to patients with HCM, who have multiple complex interrelated events leading to diastolic dysfunction. This study compares Doppler echocardiographic estimates of filling pressures to direct measurements of left atrial pressure (LAP) via catheterization in 100 patients with HCM.

Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Will there ever be a randomized trial?

Dynamic left ventricular outflow tract obstruction is an important pathophysiologic feature of hypertrophic cardiomyopathy (HCM) and a predictor of clinical deterioration and cardiovascular mortality. Patients with marked obstruction and severe limiting symptoms refractory to maximum medical management are considered candidates for invasive septal reduction therapy, which includes surgical myectomy and alcohol septal ablation (ASA). Availability of both surgical myectomy and ASA has polarized the cardiovascular community concerning the most appropriate implementation of these two interventions.

Surgery insight: Septal myectomy for obstructive hypertrophic cardiomyopathy--the Mayo Clinic experience.

Septal myectomy has been the gold standard treatment for the relief left ventricular outflow tract obstruction and cardiac symptoms in both adults and children with obstructive hypertrophic cardiomyopathy. In almost all circumstances, abnormalities of the mitral valve and subvalvar mitral apparatus can be managed without the need for mitral valve replacement, and other cardiac lesions can be repaired simultaneously. In the current era, the operative mortality for isolated septal myectomy at an experienced center is low in both children and adults (approximately 1%).

Usefulness of brain natriuretic peptide levels in the clinical evaluation of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is associated frequently with heart failure symptoms and diastolic dysfunction. Although the influence of brain natriuretic peptide (BNP) levels in the management of patients with systolic dysfunction is evolving, there are few data on the role of BNP in the management of patients with HC. BNP was compared with clinical and echocardiographic variables, including measures of diastolic filling, in 217 patients with HC.

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.

Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2.

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans.

Junctophilin-2 (JPH2) is a cardiac specific member of the junctophilins, a newly characterized family of junctional membrane complex proteins important in physically approximating the plasmalemmal L-type calcium channel and the sarcoplasmic reticulum ryanodine receptor for calcium-induced calcium release. JPH2 knockout mice showed disrupted calcium transients, altered junctional membrane complex formation, cardiomyopathy, and embryonic lethality. Furthermore, JPH2 gene expression is down-regulated in murine cardiomyopathy models.

Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy.

Aims: To determine the impact of surgical myectomy on ventricular arrhythmias in obstructive hypertrophic cardiomyopathy (HCM). Left ventricular outflow tract obstruction (LVOTO) correlates with adverse outcomes, including sudden cardiac death (SCD) in patients with HCM. Surgical myectomy is the primary treatment strategy for relief of symptoms owing to LVOTO and has been hypothesized to decrease the potential for ventricular tachyarrhythmias.

Genetics of hypertrophic cardiomyopathy: one, two, or more diseases?

Purpose Of Review: Hypertrophic cardiomyopathy is the most common identifiable cause of sudden death in the young. This review details the history of hypertrophic cardiomyopathy, recent discoveries in its genetic underpinnings and important genotype-phenotype relationships described in recent studies.

Recent Findings: Since the discovery of the genetic underpinnings of hypertrophic cardiomyopathy in 1989 hundreds of mutations scattered among at least 10 sarcomeric genes confer the pathogenetic substrate for this 'disease of the sarcomere/myofilament'.

Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota.

Background: Mechanisms purported to contribute to the pathophysiology of heart failure with normal ejection fraction (HFnlEF) include diastolic dysfunction, vascular and left ventricular systolic stiffening, and volume expansion. We characterized left ventricular volume, effective arterial elastance, left ventricular end-systolic elastance, and left ventricular diastolic elastance and relaxation noninvasively in consecutive HFnlEF patients and appropriate controls in the community.

Methods And Results: Olmsted County (Minn) residents without cardiovascular disease (n=617), with hypertension but no heart failure (n=719), or with HFnlEF (n=244) were prospectively enrolled.

Prognostic significance of exercise induced arrhythmias and echocardiographic variables in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HC) often presents with exercise-induced symptoms, including arrhythmias and sudden death. The investigators prospectively studied whether exercise testing is associated with immediate complications and if stress-induced arrhythmias and echocardiographic variables are associated with long-term adverse outcomes. Exercise echocardiography with 6-channel continuous monitoring for arrhythmias was performed in consecutive patients with HC clinically referred for the test.

Diastolic function: a sonographer's approach to the essential echocardiographic measurements of left ventricular diastolic function.

Noninvasive assessment of left ventricular filling pressures by echocardiography has been validated by invasive hemodynamic studies and correlated with clinical findings. A comprehensive echocardiographic examination based on the referral diagnosis and patient symptomatology routinely includes efforts to measure specific parameters of left ventricular diastolic function. We provide a step-by-step approach to goal-directed echocardiographic assessment of diastolic function.

Comparison of surgical septal myectomy and alcohol septal ablation with cardiac magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy.

Objectives: This study sought to describe the acute morphologic differences that result from septal myectomy and alcohol septal ablation using cardiac magnetic resonance (CMR) imaging.

Background: Surgical septal myectomy and alcohol septal ablation relieve left ventricular outflow tract obstruction in severely symptomatic patients with hypertrophic cardiomyopathy (HCM).

Methods: Cine and contrast-enhanced CMR images were obtained in HCM patients before and after septal myectomy (n = 24) and alcohol septal ablation (n = 24).

Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) can be classified into at least four major anatomic subsets based upon the septal contour, and the location and extent of hypertrophy: reverse curvature-, sigmoidal-, apical-, and neutral contour-HCM. Here, we sought to identify genetic determinants for sigmoidal-HCM and hypothesized that Z-disc-HCM may be associated preferentially with a sigmoidal phenotype. Utilizing PCR, DHPLC, and direct DNA sequencing, we performed mutational analysis of five genes encoding cardiomyopathy-associated Z-disc proteins.

Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc.

Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently, a missense mutation in the ubiquitously expressed vinculin was discovered in a patient with obstructive HCM. Microscopic examination of both myectomy specimens from patients bearing genetic defects in metavinculin and vinculin showed a marked reduction of vinculin/metavinculin expression in the intercalated disc, but normal expression in the Z-disc.

Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy.

We examined the 10-year outcome of 107 patients with hypertrophic cardiomyopathy and massive myocardial hypertrophy as assessed by echocardiography. These patients demonstrated excess mortality in comparison with their expected survival with respect to a general population of individuals (10-year survival 77% vs 95%, P < .001).

A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.

The R975W mutation, in the alternatively spliced exon 19 of vinculin (VCL) which yields the isoform metavinculin, was associated previously with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and shown to alter in vivo organization of intercalated discs. We tested the hypothesis that alterations in the ubiquitously expressed, VCL-encoded protein, vinculin, may provide a pathogenic substrate for HCM. Comprehensive mutational analysis of VCL's 22 translated exons was performed in a cohort of 228 unrelated patients with genotype negative HCM, having no identifiable mutations in 12 HCM-associated myofilament/Z-disc-encoding genes.

Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations.

Objective: To examine the relationship among age, septal morphological subtype, and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament mutations.

Patients And Methods: Comprehensive mutation analysis of the 8 HCM susceptibility genes that encode the myofilaments of the cardiac sarcomere was performed previously in 382 unrelated patients with HCM. Blinded to genotype status, we used echocardiography to characterize the left ventricular morphological features.

Prognostic utility of single-photon emission computed tomography in adult patients with hypertrophic cardiomyopathy.

Background: Data derived from stress myocardial perfusion imaging (MPI) carry prognostic significance in young patients with hypertrophic cardiomyopathy (HCM), but there are limited data on the utility of stress MPI in patients with HCM who are older. This study examined the prognostic significance of stress MPI in an adult population of patients with HCM.

Methods: We examined 158 patients with HCM (aged 60 +/- 16 years, 61% men) who underwent exercise or pharmacologic stress MPI.

Increased mitral regurgitation during the valsalva maneuver in a patient with pheochromocytoma, uncontrolled hypertension, cardiac hypertrophy, and dynamic outflow tract obstruction.

Dynamic left ventricular outflow tract obstruction is a common feature of hypertrophic cardiomyopathy, but it can also be demonstrated in other conditions that result in increased thickness of the left ventricular septal wall. Severe uncontrolled hypertension may lead to severe hypertrophy of the left ventricle and produce systolic anterior motion of the mitral valve and an outflow gradient. We report a case of pheochromocytoma with echocardiographic demonstration of markedly increased mitral regurgitation during the Valsalva maneuver in a patient with left ventricular hypertrophy and a dynamic outflow tract obstruction.