Samuela Carigi

Serial versus isolated assessment of clinical and instrumental parameters in heart failure: prognostic and therapeutic implications

BACKGROUND In heart failure (HF), it is not known whether analysis of serial changes in prognostic parameters provides incremental information with respect to comprehensive isolated clinical and instrumental assessments. METHODS We analyzed time-related changes in a period > or =6 months in a broad panel of clinical and instrumental (electrocardiographic, echocardiographic, hemodynamic, and cardiopulmonary) parameters in 105 patients with HF (age, 53 +/- 10 years; 88% men; 55% New York Heart Association classification III-IV; EF, 24% +/- 6%). RESULTS Among the time-related parameters, QRS widening (adjusted RR per 10 ms, 1.21; 95% CI, 1.10-1.48; P =.003) and peak oxygen uptake (pVO2) decrease (adjusted RR per mL/Kg/min, 1.11; 95% CI, 1.01-1.22; P =.034) provided independent, incremental information for predicting cardiac death/need for heart transplantation (CD/HT) with respect to the entire panel of isolated readings. The overall rate of CD/HT-free survival after 12 months was 60% +/- 5%. Patients who were clinically stable with QRS widening and pVO2 decrease values of <10% had a better CD/HT event-free survival rate at 1 year (92% +/- 5% vs 50% +/- 6%; P <.001). CONCLUSIONS This study indicates that analysis of time-related changes in prognostic parameters provides relevant incremental prognostic information and may help in the risk stratification of patients with HF and the selection of candidates for HT. In particular, patients who were clinically stable and had QRS widening and a pVO2 decreases <10% in a period > or =6 months appear to be characterized by a good prognosis and may not be suitable candidates for HT.

Distance between Patients’ Subjective Perceptions and Objectively Evaluated Disease Severity in Chronic Heart Failure

Background: Chronic heart failure (CHF) is a socially relevant condition carrying an adverse prognosis. Systematic analysis is needed of the relationship between quality of life (QoL) – what patients are most interested in – and objective parameters of CHF severity – which largely determines physicians’ care. Methods: We prospectively investigated QoL, as ascertained by the Minnesota Living with Heart Failure Questionnaire, alongside all the currently used objective clinical/instrumental (electrocardiographic, echocardiographic, hemodynamic and functional capacity) indicators of disease severity in 106 consecutive CHF patients. Results: Besides persistence of sinus rhythm (p = 0.007), the only objective parameters that correlated with QoL were NYHA class (p < 0.001) and distance covered during the six minutes walking test (p < 0.001) (two indications of patients’ ability to attend to their daily needs). Presence of left bundle branch block was associated with a worse QoL only in patients with CHF due to ischemic heart disease (p = 0.032). All the other clinical/instrumental parameters showed no relation with QoL (p > 0.150 in all cases). Conclusions: Objective indicators of disease severity, which largely determine physicians’ care, appear to have little bearing on QoL, suggesting that current treatment for CHF fails to satisfy patients’ perceived needs. The possibility of cost-effective nonpharmaceutical therapeutic protocols (e.g. psychological interventions) specifically designed to improve patients’ QoL deserves investigation as a much needed new approach to the management of CHF.

Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study.

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine‐lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5‐methyl‐tetrahydrofolate (n = 22), or standard therapy (control group, n = 22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra‐vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate‐treated patients (p < 0.001), coronary intimal area increased similarly in the two groups (p > 0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p < 0.04), independently from folate intake. Sub‐group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n = 19; p = 0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p = 0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia.

Effect of folate administration on heart allograft atherosclerosis one year after transplant: a prospective randomized study

or detection of a new coronary lesion after a mean observation period of 2.8 1.0 years. A multivariate analysis (backward logistic regression) was performed including potential risk factors for CAVD (see below). Patients on dialysis were excluded. Results: Initially plasma homocysteine levels were elevated in the entire cohort (mean 19.3 8.3 mol/L) and ranged from 6.6 to 56.4 mol/L. A total number of 106 patients (57,9%) presented with CAVD at first angiography and progression was detected in 51 transplant recipients (28%). Patients with progressive CAVD presented with significantly higher plasma homocysteine levels (21.7 6.3 mol/L) at baseline investigation as compared to those with a stable course (17.4 7.7 mol/L) (p 0.001). These results were independent of parameters like gender, age, time after transplantation, dyslipoproteinemia, cyclosporine blood levels, initial indication for transplantation and severity of CAVD at baseline examination. Conclusions: Progress of cardiac allograft vasculopathy is strongly associated with elevated plasma homocysteine levels. The intervals of routine surveillance angiography should be shortened in patients with hyperhomocysteinemia and medical treatment to lower elevated homocysteine is recommended in these patients.