Nishimura, Rick A.

Background— Adult patients with hypertrophic cardiomyopathy (HCM) may develop concomitant atherosclerotic coronary artery disease (CAD). There is a paucity of data on the clinical outcomes of HCM patients who have CAD. Methods and Results— We examined the outcome of 433 adult patients with HCM according to the presence and severity of CAD. All patients were aged ≥21 years, had a left ventricular ejection fraction of ≥50%, and were without a history of prior surgical revascularization (mean age, 63 years; 212 men). Compared with HCM patients with mild-to-moderate or no CAD, those with severe CAD demonstrated markedly reduced survival. Ten-year overall survival was 46.1%, 70.5%, and 77.1% for patients with severe, mild-to-moderate, and no CAD, respectively (unadjusted P =0.0001; adjusted P =0.0006). For the end point of cardiac death, this survival was 62.3%, 81.0%, and 80.9% (unadjusted P =0.009; adjusted P =0.004). For the end point of sudden cardiac death, this survival was 77.4%, 93.2%, and 90.3% (unadjusted P =0.01; adjusted P =0.01). The presence of severe CAD also was highly predictive of these events (risk ratio for respective event: 2.31, 2.15, and 2.77) in multivariate models that additionally identified age, prior stroke, hyperlipidemia, and atrial fibrillation as significant covariates. Conclusions— Among adult patients with HCM who undergo coronary angiography, those who have concomitant severe CAD are at increased risk of death. This risk far exceeds historical death rates of CAD patients with normal left ventricular function.

Background— Genotype-phenotype correlative studies have implicated 8 particular mutations that cause hypertrophic cardiomyopathy (HCM) as “benign defects,” associated with near-normal survival: N232S, G256E, F513C, V606M, R719Q, and L908V of β-myosin heavy chain ( MYH7 ); S179F of troponin T ( TNNT2 ); and D175N of α-tropomyosin ( TPM1 ). Routine genetic screening of HCM patients for specific mutations is anticipated to provide important diagnostic and prognostic information. The frequency and associated phenotype of these mutations in a large, unselected cohort of HCM is unknown. Methods and Results— A total of 293 unrelated HCM patients were genotyped for the presence of a benign mutation. DNA was obtained after informed consent; specific MHY7, TNNT2 , and TPM1 fragments were amplified by polymerase chain reaction; and the mutations were detected by denaturing high-performance liquid chromatography and automated DNA sequencing. Only 5 (1.7%) of the 293 patients possessed a benign mutation. Moreover, all 5 subjects with an ascribed benign mutation had already manifested clinically severe expression of HCM, with all 5 requiring surgical myectomy, 3 of the 5 having a family history of sudden cardiac death, and 1 adolescent requiring an orthotopic heart transplant. Conclusions— These findings demonstrate the rarity of specific mutations in HCM and challenge the notion of mutation-specific clinical outcomes. Fewer than 2% of the subjects harbored a benign mutation, and those patients with a benign mutation experienced a very serious clinical course.

Background— Although aortic valve replacement can be performed at an acceptable risk level in selected patients with left ventricular systolic dysfunction and low-output, low-gradient aortic stenosis, not all patients presenting with these hemodynamics will benefit from the operation. Some patients may have only mild aortic stenosis, despite a small calculated valve area. We report on the clinical utility of diagnostic dobutamine stimulation during cardiac catheterization in these diagnostically challenging patients. Methods and Results— Thirty-two patients with low-output, low-gradient aortic stenosis and an ejection fraction <40% had dobutamine infusion in the catheterization laboratory. On the basis of the results of the dobutamine test, 21 patients underwent aortic valve replacement. All patients with a final aortic valve area ≤1.2 cm 2 at peak dobutamine infusion and a mean gradient of >30 mm Hg were found to have severe calcific aortic stenosis at operation. In the 15 patients in whom contractile reserve was identified during dobutamine challenge (increase in stroke volume >20%), 1 patient died perioperatively (7% mortality) and 12 patients were alive in New York Heart Association class I or II status at follow-up. Conclusions— In patients with left ventricular systolic dysfunction and aortic stenosis with a low output and a low mean gradient, dobutamine challenge may aid in selecting those who would benefit from an aortic valve operation.

Background — Regional myocardial function assessment is essential in the management of coronary artery disease (CAD). Tissue Doppler imaging (TDI) by depicting local myocardial motion can potentially quantify regional myocardial function. Strain rate imaging (SRI) that depicts regional deformation is less susceptible to cardiac translation and tethering and may be superior to TDI for regional function analysis. We examined regional myocardial function using TDI and SRI in a unique clinical model of a small, discrete myocardial infarction. Method and Results — Ten patients with severely symptomatic septal hypertrophy underwent basal septal ablation via intracoronary alcohol injection and had TDI and SRI pre- and postablation. Invasive hemodynamics showed no appreciable change in global function. Peak systolic strain rate was significantly lower postablation versus preablation (−0.5 versus −1.2 s −1 , P <0.001) and when comparing infarct and noninfarct areas (−0.5 versus −1.5 s −1 , P <0.001). In contrast, peak systolic tissue velocities were similar pre- and postablation (3.9 versus 2.9 cm/s, P =0.16) and between infarct and noninfarct areas (2.9 versus 2.2 cm/s, P =0.13). SRI analysis demonstrated reduced systolic function in the peri-infarct zone and preserved systolic function in the remote nonischemic zone. Conclusion — In the clinical setting of a small, discrete infarct unaccompanied by changes in global function, SRI accurately depicted changes in regional function. These data suggest that SRI may be the optimal method for objective, quantitative assessment of regional myocardial dysfunction.