Amrit Lota

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. Methods: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. Results: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9–21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8–13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6–266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9–22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7–13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8–271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9–29.4), 4.9 (95% CI, 1.3–18.9), and 11.8 (95% CI, 4.3–32.3), respectively. Conclusions: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.

Phenotype and Clinical Outcomes of Titin Cardiomyopathy.

Background Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. Objectives The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. Methods In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. Results Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). Conclusions In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.

T2 mapping and T2* imaging in heart failure

Cardiovascular magnetic resonance (CMR) is a versatile imaging modality that enables aetiological assessment and provides additional information to that of standard echocardiography in a significant proportion of patients with heart failure. In addition to highly accurate and reproducible assessment of ventricular volumes and replacement fibrosis, multiparametric mapping techniques have rapidly evolved to further expand the diagnostic and prognostic applications in various conditions ranging from acute inflammatory and ischaemic cardiomyopathy, to cardiac involvement in systemic diseases such as sarcoidosis and iron overload cardiomyopathy. In this review, we discuss the established role of T2* imaging and rapidly evolving clinical applications of myocardial T2 mapping as quantitative adjuncts to established qualitative imaging techniques.

Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy.

To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM).

Outcome in dilated cardiomyopathy related to the extent, location and pattern of late gadolinium enhancement

Objectives This study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort. Background The relationship between LGE and prognosis in DCM is incompletely understood. Methods The authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM. Results Of 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern. Conclusions In DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.

Sudden death risk markers for patients with left ventricular ejection fractions greater than 40

The major burden of sudden cardiac death (SCD) in patients with heart disease occurs in those with a left ventricular ejection fraction > 40%. Although the annual risk of SCD may be lower in these patients compared to those with lower LVEF, their lifetime cumulative risk of SCD may be greater due to a better overall prognosis. It is plausible that those with LVEF > 40% who are at highest risk of life-threatening arrhythmia will benefit from implantable cardioverter defibrillators. Features that identify patients with a LVEF > 40% at high risk of SCD are urgently needed. We review existing studies examining SCD markers in this sub-group and discuss gaps in the current evidence base.

Osteoprotegerin and Myocardial Fibrosis in Patients with Aortic Stenosis

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).

Iatrogenic myocarditis—biomarkers, cardiovascular MRI and the need for early diagnosis

Myocarditis remains a challenging diagnosis that arises from a range of potential insults that can result in cardiac inflammation, immune activation and functional impairment [1]. Acute viral infection represents the leading aetiology followed by druginduced hypersensitivity, giant cell myocarditis and cardiac involvement in systemic autoimmune disease [2]. Due to heterogeneity in clinical presentation and disease severity, accurate epidemiological assessment is limited but overall prevalence is estimated at 22 cases per 100 000 patients annually [3]. Clozapine is the cornerstone of therapy in refractory schizophrenia and significantly reduces suicide rates further than other antipsychotic agents [4]. However, cardiotoxicity resulting in myocarditis can occur in 1–3% of patients and can result in complications including sudden cardiac death and heart failure [5, 6]. The case report by Datta and Solomon [7] describes a young patient presenting acutely with chest pain, ST segment elevation and mild troponin level elevation. Following the demonstration of unobstructed coronary arteries on invasive angiography and impaired left ventricular function on transthoracic echocardiography, a diagnosis of myocarditis likely secondary to clozapine was reached. This report emphasizes the need for prompt recognition of myocarditis and immediate withdrawal of therapy where clozapine-induced myocarditis is suspected. These features appeared 2 days after starting clozapine therapy. However, it should be noted that symptoms are often nonspecific with chest pain occurring in only half of all cases and clinical presentation varying between Days 14 and 21 after therapy initiation [8, 9]. In some cases, presentations may indeed be delayed by several months requiring a high degree of clinical suspicion for diagnosis [10]. At present, the gold standard for diagnosis of myocarditis remains an endomyocardial biopsy [11]. Histopathological analysis with immunostaining confirms the presence and characterizes the nature of acute inflammatory infiltrates. However, the limitations of endomyocardial biopsy are many and include high rates of sampling error, interobserver variability and periprocedural risks of cardiac tamponade and death. For these reasons, endomyocardial biopsy is rarely a practical first step in the diagnosis of myocarditis in the majority of centres. Cardiovascular magnetic resonance imaging (CMR) has emerged as an important diagnostic tool for the non-invasive assessment of acute myocarditis. Standard myocardial tissue characterization techniques can detect myocardial oedema, reactive hyperaemia and replacement fibrosis from myocyte cell death [12]. Diagnostic accuracy is further enhanced with novel T1 and T2 mapping approaches as shown in Fig. 1 [13]. CMR also plays an equally important role in the exclusion of other causes of troponin-positive chest pain and unobstructed coronary arteries, such as infarction due to recanalisation, spasm or embolism [14]. However, access to CMR is often limited and may be impractical as a screening test in all patients. Circulating biomarkers of myocardial injury, such as troponin, represent a more feasible initial investigation and possible approach for routine interval screening, which is relevant given that clinical presentation can be non-specific [9]. Multiple potential mechanisms have been proposed for clozapine-induced myocarditis [5]. Hypersensitivity eosinophilic myocarditis is well documented with antibiotics (37%), central nervous system agents (21%, primarily clozapine followed by carbamazepine), vaccines (8%) and a range of other

CARDIOVASCULAR MAGNETIC RESONANCE IN SURVIVORS OF SUDDEN CARDIAC ARREST: 14 YEAR EXPERIENCE FROM A TERTIARY REFERRAL CENTRE IN THE UNITED KINGDOM

Results: Of 397 patients (age 50±18yrs, 59% male) undergoing contrast enhanced CMR, rhythm disturbances were ventricular fibrillation (62%), ventricular tachycardia (8%), pulseless electrical activity/asystole (4%) and unknown (26%). In patients ≤35yrs of age (n=87), the study was normal in 52%. The most common diagnoses were dilated cardiomyopathy (14%) and acute myocarditis (10%). In patients >35yrs (n=310), myocardial infarction was found in 32% and a normal study in 26%. Late gadolinium enhancement was present in 22% ≤35yrs compared to 78% >35yrs, including 7% in both groups with an otherwise normal study.

Right Ventricle Dysfunction in Cardiomyopathy: To Measure Is to Know

I n recent years, there has been concerted effort to explore the structure and function of the right ventricle in nonischemic dilated cardiomyopathy (DCM), the second most common cause of heart failure and leading indication for cardiac transplantation. Despite a number of clinical studies, there has been a significant lag time in harnessing this information to alter patient management partly due to: 1) a lack of consensus on the threshold for clinically significant right ventricular dysfunction (RVD); and 2) a lack of data regarding its incremental value over and above left ventricular ejection fraction. Another important question is whether RVD represents a predictable consequence of severe left heart disease or rather a distinct entity amenable to established or novel therapy.