Citations

Background— Myocardial late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI and explored whether LGE among patients with HCM was associated with genetic testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD). Methods and Results— Four hundred twenty-four patients with HCM (age=55±16 years [range 2 to 90], 41% females), without a history of septal ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation between LGE and HCM genes status, severity of symptoms, and the degree of ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up of 43±14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had LGE on CE-MRI, ranging from 0.4% to 65% of the left ventricle. Gene-positive patients were more likely to have LGE ( P <0.001). The frequencies of New York Heart Association class ≥3 dyspnea and angina class ≥3 were similar in patients with and without LGE (125 of 239 [52%] versus 94 of 185 [51%] and 24 of 239 [10%] versus 18 of 185 [10%], respectively, P =NS). LGE-positive patients were more likely to have episodes of nonsustained ventricular tachycardia (34 of 126 [27%] versus 8 of 94 [8.5%], P <0.001), had more episodes of nonsustained ventricular tachycardia per patient (4.5±12 versus 1.1±0.3, P =0.04), and had higher frequency of ventricular extrasystoles/24 hours (700±2080 versus 103±460, P =0.003). During follow-up, SCD occurred in 4 patients, and additional 4 patients received appropriate ICD discharges. All 8 patients were LGE positive (event rate of 0.94%/y, P =0.01 versus LGE negative). Two additional heart failure-related deaths were recorded among LGE-positive patients. Univariate associates of SCD or appropriate ICD discharge were positive LGE ( P =0.002) and presence of nonsustained ventricular tachycardia ( P =0.04). The association of LGE with events remained significant after controlling for other risk factors. Conclusions— In patients with HCM, presence of LGE on CE-MRI was common and more prevalent among gene-positive patients. LGE was not associated with severe symptoms. However, LGE was strongly associated with surrogates of arrhythmia and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables. If replicated, LGE may be considered an important risk factor for sudden death in patients with HCM.

Background— The risk of syncope occurring while driving has obvious implications for personal and public safety. We aimed to define the clinical characteristics, causes, and prognosis of syncope while driving. Methods and Results— In this case-control study of consecutive patients evaluated for syncope from 1996 through 1998 at an academic medical center, we documented causes, clinical characteristics, and recurrence of syncope while driving. Of 3877 patients identified, 381 (9.8%) had syncope while driving (driving group). Compared with the 3496 patients (90.2%) who did not have syncope while driving, the driving group was younger ( P =0.01) and had higher percentages of male patients ( P <0.001) and patients with a history of any cardiovascular disease ( P =0.01) and stroke ( P =0.02). Syncope while driving was commonly caused by neurally mediated syncope (37.3%) and cardiac arrhythmias (11.8%). Long-term survival in the driving group was comparable to that of an age- and sex-matched cohort from the Minnesota population ( P =0.15). Among the driving group, syncope recurred in 72 patients, 35 of whom (48.6%) had recurrence >6 months after the initial evaluation. Recurrences during driving happened in 10 patients in the driving group, 7 of which (70%) were >12 months after the initial evaluation. Conclusions— In our study, neurally mediated syncope was the most common type of syncope while driving. The causes of syncope, the late recurrences of syncope (during ≥6 months of follow-up), and the overall low incidence of recurrent syncope while driving provide useful information to supplement current recommendations on driving for these patients.

Background— Mutations in myofilament proteins, most commonly MYBPC3 -encoded myosin-binding protein C and MYH7 -encoded β-myosin heavy chain, can cause hypertrophic cardiomyopathy (HCM). Despite significant advances in structure-function relationships pertaining to the cardiac sarcomere, there is limited knowledge of how a mutation leads to clinical HCM. We, therefore, set out to study expression and localization of myofilament proteins in left ventricular tissue of patients with HCM. Methods and Results— Frozen surgical myectomy specimens from 47 patients with HCM were examined and genotyped for mutations involving 8 myofilament-encoding genes. Myofilament protein levels were quantified by Western blotting with localization graded from immunohistochemical staining of tissue sections. Overall, 25 of 47 (53%) patients had myofilament-HCM, including 12 with MYBPC3-HCM and 9 with MYH7-HCM. As compared with healthy heart tissue, levels of myofilament proteins were increased in patients manifesting a mutation in either gene. Patients with a frameshift mutation predicted to truncate MYBPC3 exhibited marked disturbances in protein localization as compared with missense mutations in either MYBPC3 or MYH7 . Conclusions— In this first expression study in human HCM tissue, increased myofilament protein levels in patients with either MYBPC3 - or MYH7- mediated HCM suggest a poison peptide mechanism. Specifically, the mechanism of dysfunction may vary according to the genetic subgroup suggested by a distinctly abnormal distribution of myofilament proteins in patients manifesting a truncation mutation in MYBPC3 .