Cinzia Cianfrocca

Predictors of sudden death in idiopathic dilated cardiomyopathy

Survival in idiopathic dilated cardiomyopathy (IDC) has long been related only to left ventricular performance,1 yet there is now evidence that patients with IDC might die suddenly and unexpectedly.2,3 Although sudden death in IDC is most likely the result of a terminal malignant arrhythmia, the predictive value of complex ventricular ectopic complexes and of clinical and hemodynamic features is still controversial.4–6 We reviewed our experience with 104 consecutive patients with IDC to investigate which factors are most closely associated with sudden death.

Resting and ambulatory ECG predictors of mode of death in dilated cardiomyopathy

With the purpose of verifying whether the electrocardiogram (ECG) pattern alone can predict the mode of death in dilated cardiomyopathy, data from 12-lead ECGs and 48-hour arrhythmia monitoring were evaluated in 67 patients with dilated cardiomyopathy. During a mean follow-up period of 3 +/- 2 years, death from congestive heart failure occurred in 18 patients (27%), whereas 10 (15%) died suddenly (NS). Multivariate analysis showed that left bundle branch block (p < 0.001) and left atrial enlargement (p < 0.001) were independently related to death from congestive heart failure. Ventricular arrhythmias of Lown grade 4A or 4B (p < 0.001) and repolarization time, as assessed by QTc-QRS interval (p < 0.05), were independent predictors of sudden death. It is concluded that ECG features alone may be helpful for risk factor characterization of dilated cardiomyopathy patients, provided that multiple ECG criteria are utilized at time of diagnosis.

Histomorphometric features predict 1-year outcome of patients with idiopathic dilated cardiomyopathy considered to be at low priority for cardiac transplantation

Cardiac transplantation for patients with idiopathic dilated cardiomyopathy (IDC) and poor left ventricular function usually is postponed until symptoms have become intolerable. However, the short-term prognosis of this subset of patients has been defined poorly. Accordingly, the 1-year outcome was investigated in 30 patients with IDC with an ejection fraction < or = 25% who showed a stabilized clinical condition at assessment for transplantation and were therefore considered at low priority for surgery. During follow-up, 10 patients (group A) showed a poor outcome: 2 died suddenly, and 8 had hemodynamic failure (4 of whom underwent transplantation and 4 of whom died from heart failure while on the waiting list). The remaining 20 patients (group B) had a benign outcome. At assessment for cardiac transplantation, clinical and electrocardiographic features, left ventricular dimension, and ejection fraction were similar between the two groups. However, group A patients had higher left ventricular end-diastolic pressure (p < 0.03) and lower cardiac index (p < 0.02) and stroke volume index (p < 0.03) with respect to group B patients. In addition, the former had a lower myofibril volume fraction (p < 0.001) and a higher nuclear area (p < 0.001) compared with the latter. Multivariate analysis selected myofibril volume fraction (p < 0.001) and nuclear area (p < 0.005) as the only independent predictors of a poor 1-year outcome. The combination of myofibril volume fraction < or = 89% and nuclear area > 50 microns 2 was found in all group A patients (sensitivity 100%) but in only 2 group B patients (specificity 90%). It is concluded that in patients with IDC considered at low priority for cardiac transplantation: (1) the 1-year freedom from a cardiac event is lower than that currently expected with surgery; (2) histomorphometric features, that is, the concurrency of low myofibril volume fraction and increased nuclear area, predict short-term outcome; and (3) endomyocardial biopsy at assessment for cardiac transplantation might improve the rationalization of the timing of the procedure.

Relation of complex ventricular arrhythmias to presenting features and prognosis in dilated cardiomyopathy

To evaluate whether complex ventricular arrhythmias relate to presenting features and prognosis of dilated cardiomyopathy, 104 patients were studied from 1977 to 1987. At diagnosis, the 19 patients with complex ventricular arrhythmias (18%), as compared to the 85 patients without (82%), had a higher incidence of palpitation (P less than 0.01), severe dyspnea (P less than 0.001) and atrial fibrillation (P less than 0.01). They showed also higher mean right atrial pressures (10 +/- 5 vs 6 +/- 4 mm Hg, P less than 0.001) and higher right ventricular end-diastolic pressures (11 +/- 4 vs. 7 +/- 4 mm Hg, P less than 0.001) than patients without complex ventricular arrhythmias. Histologic samples were collected from the 32 patients (31%) studied since 1984 and semiquantitatively graded. The 11 patients with complex ventricular arrhythmias showed a higher frequency of severe interstitial fibrosis than the 21 patients without (64% vs. 24%, P less than 0.05), but they were otherwise similar as to the frequency of marked myocellular hypertrophy, changes of myocardial regression, endocardial fibrosis, attenuation of myocytes, hyperplasia of smooth muscle cells and infiltration by inflammatory cells. During a follow-up of 3.8 +/- 3.5 years, 35 patients (34%) died. Mortality was 58% (11 out of 19) in patients with complex ventricular arrhythmias and 28% (24 out of 85) in patients without (P less than 0.025). These results show that complex ventricular arrhythmias in dilated cardiomyopathy are associated with impairment of function of the right heart and severe interstitial fibrosis of the left ventricle, rather than with left ventricular dysfunction. Presence of complex ventricular arrhythmias also seems to identify those at high risk for death.

Electrocardiographic correlates with left ventricular morphology in idiopathic dilated cardiomyopathy

The purpose of the present study was to verify whether the electrocardiographic pattern of patients with idiopathic dilated cardiomyopathy (IDC) might be useful in predicting measurements of left ventricular (LV) morphology. A total of 12 electrocardiographic criteria for LV enlargement were evaluated in 67 patients with IDC, aged 14 to 68 years (mean 48), and were correlated to LV wall thickness, volume and mass, as assessed at angiography (all patients) and echocardiography (50 patients). Linear regression analysis showed weak correlations between multiple electrocardiographic criteria and LV wall thickness, volume and mass. Multiple logistic regression analysis showed that total 12-lead QRS amplitude, voltage criteria of Sokolow and Lyon, overshoot and U-wave inversion were the variables significantly related to LV wall thickness, as assessed by angiography (r = 0.55, p less than 0.005) and echocardiography (r = 0.43, p less than 0.025). The sum of T/R-wave ratios, the RV6/RV5 ratio and the Romhilt-Estes score were predictors of LV end-diastolic volume, as determined by angiography (r = 0.83, p less than 0.001) and echocardiography (r = 0.77, p less than 0.005). Total 12-lead QRS amplitude and the sum of T/R-wave ratios were the only independent predictors of LV mass, either angiographically (r = 0.81, p less than 0.001) or echocardiographically measured (r = 0.71, p less than 0.025). It is concluded that a single electrocardiographic criterion for prediction of LV morphology in patients with IDC is barely effective. Multiple electrocardiographic criteria should be utilized to better predict LV mass and distinguish reliably between LV wall thickening and dilatation.

Electrocardiographic findings in patients with hypertrophic cardiomyopathy: Relation to presenting features and prognosis

The relation of ECG findings to presenting features and prognosis was evaluated in 125 consecutive patients with hypertrophic cardiomyopathy (HC). Seventy-nine men and 46 women (mean age, 34 +/- 7 years) were studied since 1970. Most ECG features were similar in patients with and without a left ventricular outflow tract gradient. Those with obstruction had a higher prevalence of left ventricular hypertrophy according to ECG voltage criteria (54% vs. 28%, p less than 0.01), whereas higher grade ventricular arrhythmias were more common in patients without an outflow gradient (20% vs. 7%, p less than 0.05). The prevalence of ECG abnormalities was also similar in younger (less than or equal to 14 years) and older patients (greater than 14 years), and only repolarization abnormalities were more frequently detected in the older age group (56% vs. 32%, p less than 0.025). Stratification of patients according to the clinical state revealed that those who had moderate to severe functional limitation had a higher prevalence of atrial fibrillation than asymptomatic or mildly symptomatic patients (24% vs. 1%, p less than 0.001). There were no significant differences in most hemodynamic variables among patients dichotomized according to any specific ECG abnormality. Only patients with atrial fibrillation had significantly higher right ventricular end-diastolic pressure (10 +/- 7 vs. 6 +/- 4 mmHg, p less than 0.01), lower systolic index (22 +/- 8 vs. 37 +/- 15 ml/m2; beat, p less than 0.02) and lower ejection fraction (53 +/- 8 vs. 64 +/- 10%, p less than 0.001) than those in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertrophic cardiomyopathy: Long-term effects of propranolol versus verapamil in preventing sudden death in “low-risk” patients

SummaryThe aim of this study was to evaluate retrospectively the outcome of 101 patients who were assigned to longterm therapy with propranolol (55 patients) or verapamil (46 patients) between 1980 and 1988. Baseline clinical, electrocardiographic, and echocardiographic data were similar in both groups. Exclusion criteria were the evidence of complex ventricular arrhythmias, a family history of the disease and/or sudden death, previous syncopal episodes, or left ventricular dysfunction. During a mean follow-up of 4±3 years (range: 1–9 years), side effects were more commonly recorded in patients who were treated with verapamil rather than in propranolol-treated patients (8 vs. 3,rrespectively), though the difference was not statistically significant. Sixteen patients (13 propranolol-treated patients and three verapamiltreated ones, p<0.05) died suddenly while on treatment. In addition, three patients who stopped verapamil because of adverse reactions died from heart failure after withdrawal, but before the end of the follow-up period. The assessment of total mortality on the intention-to-treat basis showed that death due to cardiac causes occurred in 13 propranololtreated patients and in six verapamil-treated patients (ns). Thus, verapamil was more effective than propranolol in preventing sudden death during long-term therapy of “low-risk” patients with hypertrophic cardiomyopathy, though its administration was associated with the occurrence of nonsudden cardiac deaths and a high incidence of side effects.

Natural history of hypertrophic cardiomyopathy in the elderly.

To assess the natural history of hypertrophic cardiomyopathy (HC) in the elderly, we reviewed clinical, electrocardiographic and hemodynamic data from 21 patients over 60 years of age at diagnosis who were studied since 1970. Comparison with 95 younger patients (less than 60 years) showed that a greater proportion of older patients had exertional angina and atrioventricular conduction delay at time of diagnosis. During a mean follow-up of 9 +/- 6 years, mortality from cardiac causes was 33% (7 out of 21) in patients over 60 years of age and 23% (22 out of 95) in younger patients (NS). Univariate analysis showed that functional class and hemodynamic indices of right- and left-sided heart impairment were associated with a poor prognosis in the elderly. We conclude that: (1) presenting features and outcome of patients with HC over 60 years of age do not differ significantly from those of younger patients; (2) functional class and measurements of cardiac function are significant predictors of death in the elderly.

The progression of hypertrophic cardiomyopathy: dilatation of the left ventricle with supernormal systolic function

We performed cardiac catheterisation in a man who had been diagnosed as having hypertrophic cardiomyopathy 7 years earlier. The repeat angiogram showed the maintenance of a supernormal systolic function (ejection fraction: 87%) although there was an increase of left ventricular end-diastolic volume (from 65 to 132 ml/m2). This case suggests that progressive left ventricular dilatation should not necessarily be considered a marker of the progression of hypertrophic cardiomyopathy into a hypokinetic left ventricle.

Acute effects of nifedipine versus isosorbide dinitrate on exercise tolerance in patients with isolated coronary artery occlusion and collaterals

SummaryThe acute effects of slow-release nifedipine and isosorbide dinitrate on exercise tolerance were compared in nine patients with isolated total coronary artery occlusion showing retrograde filling via collaterals. All patients had a reproducible positive exercise stress test off medication before the study. Each patient was randomized to 10 mg slow-release nifedipine and 5 mg isosorbide dinitrate in a single-blind, cross-over study. The exercise stress test was performed 30 minutes after drug administration. After nifedipine, three patients had a negative exercise stress test, whereas the test was negative after isosorbide dinitrate only in one patient. A significantly higher exercise tolerance was detected at peak exercise after nifedipine than after isosorbide dinitrate, as shown by a longer exercise time (380±44 vs. 295±41 seconds, p<0.001), a more increased maximum work load (355±89 vs. 255±55 W/min. p<0.02), and a higher rate-pressure product (30,300±2,500 vs. 26,100±2,700, p<0.01). In conclusion, these results seem to suggest that nifedipine may have a vasomotor effect on collaterals, since it elevated the threshold of ischemia more than isosorbide dinitrate did in patients with isolated coronary artery occlusion, showing retrograde filling via collaterals.