hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) patients have a predisposition for malignant VT/VF and consequently, sudden cardiac death (SCD). In single center studies, late gadolinium enhancement (LGE) defined fibrosis has been linked to VT/VF. However, despite innumerable investigations, SCD has not been definitely attributable to LGE. Explanations for these are believed to be related to insufficient statistical power. Methods: We performed an electronic search of MEDLINE, PubMed: and CMR abstracts for original data published or presented between Jan 2001 to Mar 2011. Key search terms: HCM, LV fibrosis, SCD and LGE. Studies were screened for eligibility based on inclusion criteria: referral for CMR exam with LGE for HCM; and follow-up for incidence of VT/VF and SCD. Categorical variables were evaluated between patient groups via Chi-square test. Results: A total of 64 studies were initially identified. Of these, 4 (6.3%) were identified and included (n = 1063 patients). Three prospective and one retrospective study were included. LGE was detected in 59.6% of patients. As expected, the presence of myocardial fibrosis was associated with VT/VF (x2 = 6.5, p < 0.05; OR 9.0, (95% CI 1.2 to 68.7). Moreover, myocardial fibrosis strongly predicted SCD (x2 = 6.6, p < 0.05; OR 3.3 (95% CI 1.2 to 9.7). Conclusion: Despite single center CMR studies, LGE has consistently predicted VT/VF while prediction of SCD has remained paradoxically unlinked. Although the lack of studies meeting our criteria limited our ability to perform a comprehensive meta-analysis, we have been able to demonstrate for the first time that LGE-defined fibrosis is a predictor of SCD in patients with HCM0.

The normal adult heart is a well maintained machine that has a mechanism for growth replacement of the sarcomere that is lost by natural degeneration. This process ensures the heart has the strength of contraction to function correctly giving blood supply to the whole body. Some of the force of contraction of the sarcomere is transmitted to its major protein titin where its strength results in unfolding of a flexible section and release of a growth stimulant. The origin of all the cardiomyopathies can be traced to errors in this system resulting from mutations in a wide variety of the sarcomeric proteins. Too much or chronic tension transfer to titin giving increased growth resulting in hypertrophic cardiomyopathy (HCM) and too little leading to muscle wastage, dilated cardiomyopathy (DCM). HCM can ultimately lead to sudden cardiac death and DCM to heart failure. In this paper I show (1) a collection of the tension/ATPase calcium dependencies of cardiac myofibrils that define the mechanism of Ca2+ cooperativity. (2) I then reintroduce the stress/strain relationship to cardiomyopathies. (3) I then review the cardiomyopathy literature that contains similar Ca2+ dependency data to throw light on the mechanisms involved in generation of the types of myopathies from the mutations involved. In the review of cardiomyopathy there are two sections on mutations, the first dealing with those disrupting the Ca2+ cooperativity, i.e. the Hill coefficient of activation, leading to incomplete relaxation in diastole, chronic tension, and increased growth. Secondly dealing with those where the Ca2+ cooperativity is not affected giving either increased or decreased tension transfer to titin and changes in sarcomere growth. 

Left ventricular outflow tract obstruction is a well-recognized feature in hypertrophic cardiomyopathy but can occur in other clinical scenarios when anatomically susceptible heart is subjected to permissive physiological conditions that provoke systolic anterior motion of the mitral valve (SAM): ie, reduced preload, increased inotropic state, and decreased afterload. This report describes a case of hemodynamically significant latent LVOTO that was associated with hypotension, syncope, acute myocardial ischemic ECG changes, and an increase in cardiac enzymes. (Type II myocardial infarction) in a non HCM patient with excessive anterior mitral valve tissue.