E. Douglas Wigle

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

A 29-year-old Dominican man with a history of intravenous heroin use and hepatitis C presented with a 5-day history of fever, dyspnoea, haemoptysis, pleuritic chest pain, abdominal pain, haematochezia and haematemesis. Initial physical examination was significant for scleral icterus, generalised abdominal tenderness to palpation, melaena and blood-tinged sputum. Blood cultures grew Fusobacterium species. CT scan of the chest revealed multiple bilateral cavitary features in lung fields. At the same time, a neck ultrasound performed demonstrated thrombophlebitis in the right internal jugular vein, confirming the diagnosis of ‘Lemierre’s syndrome’. Treatment was with antibiotics and supportive care for 6 weeks.

Long-Term Outcome in Patients With Apical Hypertrophic Cardiomyopathy

OBJECTIVES The aim of this study was to describe long-term outcome in patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a tertiary referral center. BACKGROUND Apical hypertrophic cardiomyopathy is a relatively rare form of hypertrophic cardiomyopathy (HCM), first described in Japan. Initial reports, based on a limited number of patients, emphasized the benign nature of this condition. METHODS A retrospective study of 105 patients with ApHCM diagnosed at the Toronto General Hospital from 1975 to 2000 was performed. Symptoms, clinical findings, mortality and cardiovascular morbidity were analyzed. RESULTS The mean age at presentation was 41.4 +/- 14.5 years. During a mean follow-up of 13.6 +/- 8.3 years from presentation, cardiovascular mortality was 1.9% (2/105) and annual cardiovascular mortality was 0.1%. Overall survival was 95% at 15 years. Thirty-two patients (30%) had one or more major morbid events, the most frequent being atrial fibrillation (12%) and myocardial infarction (10%). Probability of survival without morbid events was 74% at 15 years. Three predictors of cardiovascular morbidity were identified: age at presentation <41 years, left atrial enlargement, and New York Heart Association (NYHA) class > or = II at baseline. Forty-four percent of the patients were asymptomatic at the time of last follow-up. CONCLUSIONS Apical hypertrophic cardiomyopathy in North American patients is not associated with sudden cardiac death and has a benign prognosis in terms of cardiovascular mortality. Nevertheless, one third of these patients experience serious cardiovascular complications, such as myocardial infarction and arrhythmias. These data are likely to influence the counseling and management of patients with ApHCM.

Clinical and Echocardiographic Determinants of Long-Term Survival After Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy

Background—Surgical myectomy has been the standard treatment for patients with drug-refractory obstructive hypertrophic cardiomyopathy. The clinical and echocardiographic predictors of long-term survival and freedom from cardiovascular morbidity after myectomy have been unclear. Methods and Results—We studied a consecutive cohort of 338 adult patients (age at operation 47±14 [range 18 to 77] years, 60% male) who underwent myectomy at our institution. Preoperative resting left ventricular outflow tract (LVOT) gradient was 66±32 mm Hg (range 5 to 158 mm Hg). Early postoperative mortality was 1.5% (5 deaths): 4 deaths occurred between 1978 and 1992, and 1 death occurred between 1993 and 2002. During long-term follow-up, 83% of patients reported an improvement to functional class I or II. The majority of patients (98%) had no resting LVOT gradient. Long-term survival was excellent, with 98±1% survival at 1 year, 95±1% at 5 years, and 83±3% at 10 years after myectomy. Multivariable Cox regression analysis identified 5 predictors of overall mortality: (1) age ≥50 years at surgery (hazard ratio [HR] 2.8, 95% CI 1.5 to 5.1, P=0.001), (2) female gender (HR 2.5, 95% CI 1.5 to 4.3, P=0.0009), (3) history of preoperative atrial fibrillation (HR 2.2, 95% CI 1.2 to 4.0, P=0.008), (4) concomitant CABG (HR 3.7, 95% CI 1.7 to 8.2, P=0.001), and (5) preoperative left atrial diameter ≥46 mm (HR 2.9, 95% CI 1.6 to 5.4, P=0.0008). Significant predictors of late major cardiovascular events found on multivariable analysis were (1) female gender (HR 3.3, 95% CI 2.0 to 5.4, P<0.0001), (2) history of preoperative atrial fibrillation (HR 1.9, 95% CI 1.1 to 3.3, P=0.02), and (3) preoperative left atrial diameter ≥46 mm (HR 2.5, 95% CI 1.5 to 4.3, P=0.0008). Conclusions—Myectomy provides excellent relief for LVOT obstruction in patients with hypertrophic cardiomyopathy. Preoperative clinical and echocardiographic variables can predict long-term outcome after myectomy.

Idiopathic Ventricular Septal Hypertrophy Causing Muscular Subaortic Stenosis

The clinical, hemodynamic, angiographic and, where available, surgical and postmortem findings of 10 cases of muscular subaortic stenosis have been reviewed and, from the evidence at hand, it would appear that the majority of these cases had as the basis for the stenosis, idiopathic ventricular septal hypertrophy (asymmetrical hypertrophy of the heart).3 This septal muscle mass leads to obstruction of the right as well as the left ventricular outflow tract, in addition to impeding diastolic ventricular filling as a result of low ventricular compliance. These features give rise to a unique clinical, hemodynamic, and angiographic picture.

The 50-Year History, Controversy, and Clinical Implications of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: From Idiopathic Hypertrophic Subaortic Stenosis to Hypertrophic Cardiomyopathy

Dynamic obstruction to left ventricular (LV) outflow was recognized from the earliest (50 years ago) clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon unique in many respects, as well as arguably the most visible and well-known pathophysiologic component of this heterogeneous disease. Over the past 5 decades, the clinical significance attributable to dynamic LV outflow tract gradients in HCM has triggered a periodic and instructive debate. Nevertheless, only recently has evidence emerged from observational analyses in large patient cohorts that unequivocally supports subaortic pressure gradients (and obstruction) both as true impedance to LV outflow and independent determinants of disabling exertional symptoms and cardiovascular mortality. Furthermore, abolition of subaortic gradients by surgical myectomy (or percutaneous alcohol septal ablation) results in profound and consistent symptomatic benefit and restoration of quality of life, with myectomy providing a long-term survival similar to that observed in the general population. These findings resolve the long-festering controversy over the existence of obstruction in HCM and whether outflow gradients are clinically important elements of this complex disease. These data also underscore the important principle, particularly relevant to clinical practice, that heart failure due to LV outflow obstruction in HCM is mechanically reversible and amenable to invasive septal reduction therapy. Finally, the recent observation that the vast majority of patients with HCM have the propensity to develop outflow obstruction (either at rest or with exercise) underscores a return to the characterization of HCM in 1960 as a predominantly obstructive disease.

Systolic Myocardial Mechanics in Hypertrophic Cardiomyopathy : Novel Concepts and Implications for Clinical Status

In hypertrophic cardiomyopathy (HCM), malfunctioning sarcomeric protein, myocyte hypertrophy, fiber disarray, and interstitial fibrosis interfere with systolic myocardial mechanics despite clinically hyperdynamic systolic function. We evaluated local left ventricular (LV) mechanics in 72 patients with HCM and 32 control subjects using 2-dimensional velocity vector imaging. Patients had higher circumferential strain (-34 +/- 9 vs -29 +/- 8, P < .05) and lower longitudinal strain (-16 +/- 4 vs -21 +/- 4, P < .05) compared with control subjects. Biplanar strain vector magnitude was similar (-38% +/- 8 vs -36 +/- 7) in both groups, but was circumferentially oriented in HCM (27 +/- 10 vs 39 +/- 9 degrees, P < .05). Mid LV rotation was clockwise (opposite to normal). LV outflow tract obstruction and clinical status were related to more circumferentially directed strain and reduced apical biplanar strain. Patients with HCM have more circumferential myocardial strain and apically displaced systolic twist. Functional status and LV outflow tract obstruction were related to decreased strain vector angle and apical mechanics. These findings provide insights into the pathophysiology of HCM.

Transesophageal Doppler echocardiography in obstructive hypertrophic cardiomyopathy: clarification of pathophysiology and importance in intraoperative decision making.

To better understand the pathophysiology of obstruction of left ventricular outflow in hypertrophic cardiomyopathy and to determine the value of intraoperative transesophageal Doppler echocardiography in decision making, 32 consecutive patients undergoing ventriculomyectomy were assessed. The mean preoperative left ventricular outflow gradient was 83 +/- 39 mm Hg and the mean basal septal width was 24 +/- 6 mm. Compared with transesophageal findings in 10 normal control subjects, the mitral leaflets were longer and the coaptation point was abnormal in the patients with obstructive hypertrophic cardiomyopathy (anterior and posterior leaflet lengths in the patients were 31 +/- 4 vs. 22 +/- 3 mm in the control group [p less than 0.00001] and 20 +/- 2 vs. 15 +/- 3 mm in the control group [p less than 0.00001]). The coaptation point in the patient group was in the body of the leaflets at a mean of 9 +/- 2 mm from the anterior leaflet tip, whereas it was at or within 3 mm of the leaflet tip in the normal group. During early systole, the distal third to half of the anterior mitral leaflet angled sharply anteriorly and superiorly (systolic anterior motion), resulting in leaflet-septal contact and incomplete mitral leaflet coaptation in mid-systole. This caused the formation of a funnel, composed of the distal parts of both leaflets, that allowed a jet of posteriorly directed mitral regurgitation to occur in mid- and late systole. The sequence of events in systole was eject/obstruct/leak. Transesophageal echocardiography was also helpful in planning the extent of the resection, assessing the immediate result and excluding important complications. In successful cases, the post-myectomy study showed 1) a dramatic thinning of the septum, with widening of the left ventricular outflow tract to a width similar to that in the normal subjects, 2) resolution of systolic anterior motion and the left ventricular outflow tract color mosaic, and marked reduction or abolition of mitral regurgitation despite persistence of abnormal mitral leaflet length and an abnormal mitral leaflet coaptation point. The routine use of transesophageal echocardiography in patients undergoing surgical myectomy for the treatment of obstructive hypertrophic cardiomyopathy is recommended.

Role of Echocardiography in Diagnostic and Hemodynamic Assessment of Hypertrophic Subaortic Stenosis

An abnormal sharp anterior motion of the anterior mitral leaflet has been previously described as a diagnostic abnormality in hypertrophic subacute stenosis (HSS). The present prospective study explored the diagnostic sensitivity and specificity of this finding in 26 patients studied without knowledge of clinical diagnosis. When the abnormality observed was complete and persistent, a correct diagnosis of HSS was made in every case. In the absence of systolic abnormality at rest and on provocation, the diagnosis of HSS could be excluded. When the abnormality was small and inconstant (nine patients) two thirds of the patients were shown to have a latent or labile form of outflow obstruction whereas the remaining third had no evidence of HSS.In an extended part of the study on 31 patients with known HSS, comparisons of resting pressure gradients across left ventricular outflow tract were made with the echocardiographic findings at rest. Those with persistently abnormal mitral valve movement had an average pressure gradient of 78 mm Hg, those with inconstant abnormality had an average gradient of 24 mm Hg, and those with no resting abnormality had no gradients at rest.

Hypertrophic cardiomyopathy: Subclassification by M mode echocardiography

Abstract Seventy-four patients with hypertrophic cardiomyopathy, hemodynamically classified into well defined subgroups (left ventricular outflow tract obstruction at rest [27 patients], labile obstruction [4 patients], latent obstruction [28 patients] and no obstruction [15 patients]) were studied with M mode echocardiography. Significant echocardiographic differences were found among these groups. The most important differentiating feature was the degree of systolic anterior motion of the anterior mitral leaflet. Combined with prolonged interventricular septal contact (that is, for more than 30 percent of echocardiographic systole), it occurred in all 27 patients with obstruction at rest but in no patient with latent or no obstruction. Another differentiating feature was aortic valve midsystolic notching, which occurred in all 25 patients with obstruction at rest (in whom adequate aortic valve echograms could be obtained) but in only 3 of 17 patients with latent obstruction and in no patients without obstruction. The third most useful differentiating feature was left atrial enlargement, which occurred in 25 of 27 in the group with obstruction at rest, but in only 4 of 28 in the group with latent obstruction and in 2 of 15 in the group without obstruction. Other M mode echocardiographic findings in patients with hypertrophic cardiomyopathy showed overlap among subgroups and therefore could not be relied on for noninvasive subclassification. These echocardiographic abnormalities included septal and posterior wall thickness, septum to posterior wall thickness ratio, septal and posterior wall systolic thickening, left ventricular internal diameter, left ventricular outflow tract size at the onset of systole, mitral leaflet position and percent diastolic anterior mitral leaflet-interventricular septal contact. It is concluded that a noninvasive classification of patients with hypertrophic cardiomyopathy into hemodynamic subgroups of obstruction at rest, latent obstruction and no obstruction can be made by assessing the degree of systolic anterior motion, the presence of aortic valve mid systolic notching, and left atrial size. This noninvasive M mode echocardiographic subclassification has important clinical implications.

Muscular Subaortic Stenosis Initial Left Ventricular Inflow Tract Pressure in the Assessment of Intraventricular Pressure Differences in Man

Two types of intraventricular pressure difference within the left ventricle of man are described. The first type was encountered in eight consecutive patients with muscular subaortic stenosis in whom the outflow tract pressure distal to the stenosis was low and equal to the aortic systolic pressure, whereas all ventricular pressures proximal to the stenosis, including that just inside the mitral valve (the initial inflow tract pressure) were high. The second type was encountered in five of 10 patients with nonobstructive cardiomyopathy when a cardiac catheter was advanced to the left ventricular wall where it became entrapped or imbedded in cardiac muscle in systole and recorded a high ventricular pressure that was believed to reflect subendocardial intramyocardial tissue pressure. In this second type of intraventricular pressure difference, the initial inflow tract pressure, as well as all truly intracavitary pressures, were low and equal to the aortic systolic pressure.By defining two types of intraventricular pressure difference, the recent controversy as to the nature of such pressure differences in man may be resolved, and the obstructive nature of muscular subaortic stenosis reaffirmed.