Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is an important cause of heart failure-related disability over a wide range of ages. Profiles of severe progressive heart failure symptoms and death, or heart transplantation deserve more complete definition within large patient cohorts. METHODS AND RESULTS: Clinical and morphological features of heart failure were assessed in 293 consecutive HCM patients over a median follow-up of 6 (inter-quartile range 2-11) years. Gross and histopathological features were analysed in 12 patients for whom the heart was available for inspection. Of the 293 patients, 50 (17%) developed severe progressive heart failure, including 18 who died or were transplanted. Three profiles of heart failure were identified predominantly associated with: (i) end-stage systolic dysfunction (ejection fraction <50%) (15; 30%); (ii) left ventricular (LV) outflow obstruction at rest (11; 22%); and (iii) non-obstructive with preserved systolic function (24; 48%). Overall, atrial fibrillation (AF) contributed to heart failure in 32 patients (64%) among the three profiles. Compared with other patients, those non-obstructive with preserved systolic function had earlier onset of heart failure symptoms mainly due to diastolic dysfunction, and the most accelerated progression to advanced heart failure and adverse outcome (P = 0.04). Thrombi were identified in the left atrial appendage of five gross heart specimens all belonging to patients with AF, including three of which were unrecognized clinically and had previously embolized. Extensive myocardial scarring with LV remodelling was evident in all end-stage patients; no or only focal scars were present in other patients. CONCLUSION: Profiles of advanced heart failure in HCM are due to diverse pathophysiological mechanisms, including LV outflow obstruction and diastolic or global systolic ventricular dysfunction. Atrial fibrillation proved to be the most common disease variable associated with progressive heart failure. Recognition of the heterogeneous pathophysiology of heart failure in HCM is relevant, given the targeted management strategies necessary in this disease.

Three-dimensional electroanatomical voltage mapping and histologic evaluation of myocardial substrate in right ventricular outflow tract tachycardia.

OBJECTIVES: We tested whether 3-dimensional electroanatomical voltage mapping (EVM) may help in the differential diagnosis between idiopathic right ventricular outflow tract (RVOT) tachycardia and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). BACKGROUND: Right ventricular EVM has been demonstrated to reliably identify low-voltage regions ("electroanatomical scar"), which in patients with ARVC/D correspond to areas of fibrofatty myocardial replacement. METHODS: The study population comprised 27 patients (15 men and 12 women, age 33.9 +/- 8 years) with RVOT tachycardia and no echocardiographic/angiographic evidence of right ventricular (RV) dilation/dysfunction, who underwent EVM and endomyocardial biopsy (EMB) for characterization of ventricular tachycardia (VT) substrate before catheter ablation. RESULTS: Electroanatomical voltage mapping was normal in 20 of 27 patients (74%, group A), with electrogram voltage >1.5 mV throughout the RV. The other 7 patients (26%, group B) showed >/=1 (1.4 +/- 07) RV electroanatomical scar area(s) (bipolar voltage <0.5 mV) that correlated with fibrofatty myocardial replacement at EMB (p < 0.001). Clinical predictors of RV scar were right precordial QRS prolongation (p < 0.001) and VT inducibility (p = 0.001). Catheter ablation successfully eliminated VT in 18 of 20 patients (90%). During a follow-up of 41 +/- 8 months, 3 of 7 patients (43%) from group B received an implantable defibrillator because of life-threatening ventricular arrhythmias, compared with no patients from group A (p = 0.016). CONCLUSIONS: An early/minor form of ARVC/D may mimic idiopathic RVOT tachycardia. Electroanatomical voltage mapping is able to identify RVOT tachycardia due to concealed ARVC/D by detecting RVOT electroanatomical scars that correlate with fibrofatty myocardial replacement at EMB and predispose to sudden arrhythmic death.

Three-dimensional electroanatomic voltage mapping increases accuracy of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Three-dimensional electroanatomic voltage mapping offers the potential to identify low-voltage areas that correspond to regions of right ventricular (RV) myocardial loss and fibrofatty replacement in patients with arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). METHODS AND RESULTS: Thirty-one consecutive patients (22 men and 9 women; mean age, 30.8+/-7 years) who fulfilled the criteria of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D diagnosis after noninvasive clinical evaluation underwent further invasive study including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175+/-23) were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal RV electroanatomic voltage mapping showing > or =1 area (mean 2.25+/-0.7) with low-voltage values (bipolar electrogram amplitude <0.5 mV), surrounded by a border zone (0.5 to 1.5 mV) that transitioned into normal myocardium (>1.5 mV). Low-voltage electrograms appeared fractionated with significantly prolonged duration and delayed activation. In 11 patients (group B; 35%), electroanatomic voltage mapping was normal, with preserved electrogram voltage (4.4+/-0.7 mV) and duration (37.2+/-0.9 ms) throughout the RV. Low-voltage areas in patients from group A corresponded to echocardiographic/angiographic RV wall motion abnormalities and were significantly associated with myocyte loss and fibrofatty replacement at EMB (P<0.0001) and familial ARVC/D (P<0.0001). Patients from group B had sporadic disease and histopathological evidence of inflammatory cardiomyopathy (P<0.0001). During the time interval from onset of symptoms to the invasive study, 11 patients (55%) with electroanatomic low-voltage regions received an implantable cardioverter/defibrillator because of life-threatening ventricular arrhythmias, whereas all but 1 patient with a normal voltage map remained stable on antiarrhythmic drug therapy (P=0.02). CONCLUSIONS: Three-dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing ARVC/D (1) by demonstrating low-voltage areas that were associated with fibrofatty myocardial replacement and (2) by identifying a subset of patients who fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a better arrhythmic outcome.

Autonomic modulation and clinical outcome in patients with chronic heart failure.

OBJECTIVE: Several studies documented the relevance of autonomic activity in the pathophysiology of heart failure. In our study we evaluated the adjustment of this activity under different stimuli, by means of heart rate variability (HRV), and correlated these findings with long-term mortality and sustained VT occurrence. PATIENTS AND METHOD: Fifty-three patients (mean age 54+/-9 years) with heart failure were submitted to time and frequency domain HRV analysis. This latter analysis was performed at rest, during paced breathing and during passive tilt. RESULTS: Lower standard deviation of RR intervals (76.76+/-24 versus 107.70+/-43, p=0.02), mean of the 5-min standard deviations of RR intervals (35.14+/-15 versus 62.39, p<0.01), standard deviation of the 5-min average RR intervals (69.42+/-19 versus 91.79+/-30, p=0.02), and baseline Low-Frequency (LF) power (15.15+/-12 versus 40.39+/-24 nu, p=0.001) characterized patients who died. Paced breathing induced a significant reduction of LF (40.39+/-24 to 20.12+/-18 nu, p<0.0001) and increase of High Frequency power (HF) (47.31+/-23 to 70.63+/-16 nu, p<0.0001) in survivors, while tilting induced a reduction of HF (47.31+/-23 to 29.80+/-16 nu, p<0.0001). Patients who died did not show significant variation of HRV neither during paced breathing nor during tilt. Reduced time domain indexes were significantly correlated to sustained VT occurrence. CONCLUSIONS: Patients with heart failure with a better prognosis are characterized by a responsiveness of autonomic modulation. Simple maneuvers, such as tilting and paced breathing, seem to provide more useful information, than the baseline evaluation of autonomic status, in identifying patients with a higher mortality. Time domain analysis was more helpful to estimate arrhythmic risk.