BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Monophasic action potentials (MAPs) were recorded with intracardiac suction electrodes in several areas of the right ventricle in 10 patients with long QT syndromes (with "torsades de pointe') of different etiology. In all cases two characteristic electrophysiological features were observed: (1) a marked difference in MAP duration in the different areas of the right ventricle (asynchronous repolarization); (2) an alteration in the shape of the longest MAPs consisting in humps which occurred on the repolarization phase of MAP. Humps may be interpreted as delayed repolarization phenomena probably due to a decrease in potassium conductance of some ventricular cells. These may lead to focal re-excitation as a result of partial membrane depolarization. Focal re-excitation seems to play a key role in the genesis of severe arrhythmias occurring in the above mentioned syndromes.

In 58 human subjects monophasic action potentials (MAPs) were recorded with suction electrodes in several areas of the right ventricle (RV). Individual differences between the longest and the shortest RV MAP durations indicate that: normally (40 subjects) ventricular repolarization is almost synchronous; QT prolongation due either to bradycardia or to amiodarone treatment (eight cases) may be the result of a uniform lengthening of ventricular repolarization, when ventricular arrhythmias are not present; in long QT syndromes (LQTSs) of differing etiology (10 cases), in which severe ventricular arrhythmias are present, marked individual differences in RV MAP duration are present and correspond with pathological asynchrony of ventricular repolarization. Also observed in the LQTSs are morphological alterations (humps) in the terminal phase of the longest MAPs. Humps, interpreted as pathological delayed repolarization phenomena, may lead to focal re-excitation which seems to play a key role in the genesis of the arrhythmias complicating LQTSs.

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