ABSTRACT
OBJECTIVES: We sought to investigate whether erectile dysfunction (ED) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease (CAD) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED. BACKGROUND: Case-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available. METHODS: Type 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire. RESULTS: During a follow-up period of 47.2 +/- 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p = 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p < 0.001). Among patients with CAD and ED, the Kaplan-Meier method showed that the statin (Mantel log-rank test: 3.921; p = 0.048) and 5-phosphodiesterase (5-PDE) inhibitor use (Mantel log-rank test: 4.608; p = 0.032) were associated with a lower rate of MACE. Cox regression analysis showed that statin use (HR 0.66; 95% CI 0.46 to 0.97; p = 0.036) reduced MACE. Treatment with 5-PDE inhibitors did not enter the model, but its p value was very near to the significant level (HR 0.68; 95% CI 0.46 to 1.01; p = 0.056). CONCLUSIONS: Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED.
Subject(s)
Cardiovascular Diseases/etiology , Coronary Artery Disease/complications , Diabetes Mellitus, Type 2/complications , Erectile Dysfunction/complications , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Phosphodiesterase Inhibitors/therapeutic use , Cardiovascular Diseases/mortality , Cardiovascular Diseases/prevention & control , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Risk FactorsABSTRACT
BACKGROUND: Patients with AL amyloidosis often present with signs of congestive heart failure. AIM: This study was prospectively designed to assess the significance of RV dysfunction in AL amyloidosis. METHODS AND RESULTS: Seventy-four patients with biopsy proven AL amyloidosis underwent a thorough echocardiographic evaluation. A tricuspid annular plane systolic excursion (TAPSE)<17 mm was taken as marker of RV dysfunction. Plasma NT-proBNP determinations were performed in all cases. RV function was normal in 60 patients and reduced in 14 patients. Patients with RV dysfunction had thicker left ventricular (LV) walls (p<0.01), lower LV end-diastolic volumes (p<0.01), lower LV ejection fraction (p<0.01) and more frequently a restrictive LV filling pattern (p<0.01). RV dimensions and RV free wall thickness were not significantly different in the two groups. A thick interventricular septum and a reduced TAPSE were associated with high NT-proBNP levels (both p<0.01). Seven patients died during a median follow-up period of 19 months; TAPSE<17 mm was the only echocardiographic parameter associated with poor survival. CONCLUSION: In patients with AL amyloidosis, RV dysfunction is associated with more severe involvement of the left ventricle, higher plasma levels of NT-proBNP and with poor prognosis.
Subject(s)
Amyloidosis/physiopathology , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Function, Right , Adult , Aged , Echocardiography, Doppler , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , Prospective Studies , Stroke Volume , Ventricular Dysfunction, LeftABSTRACT
We observed previously that in rats with aortic banding (Bd), development of left ventricular (LV) hypertrophy is opposed by beta-blockade, whereas interventions interfering with alpha-adrenoceptor function also inhibit interstitial fibrosis. To assess whether these differential structural effects do translate into different effects on LV function and on heart failure mortality, Bd or sham Bd 8-week-old rats were randomized to vehicle treatment (Vh), chemical sympathectomy ([Sx] 6-hydroxydopamine, 150 mg/kg IP twice a week), beta-adrenoceptor blockade (propranolol [Pro], 40 mg/kg per day PO), or alpha-adrenoceptor blockade (doxazosin [Dox], 5 mg/kg per day PO). After monitoring survival for 10 weeks, the survivors were anesthetized to undergo echocardiography and intraarterial blood pressure measurement. Bd-Vh rats showed increased LV and lung weights, as well as LV dilation, depressed endocardial and midwall fractional shortening and a restrictive transmitral diastolic flow velocity pattern. Compared with Bd-Vh rats, all of the actively treated Bd rats showed less LV hypertrophy, LV dilation, and lung congestion but no less depression of midwall fractional shortening. In contrast, Sx and Dox but not Pro treatment were also associated with lesser degrees of diastolic dysfunction and, even more importantly, with a striking increase in survival (sham banded rats, 100%; Bd-Vh, 40%; Bd-Pro, 51%; Bd-Sx, 83%; and Bd-Dox, 82%). Although Pro, Sx, and Dox provide similar midterm protection from development of LV hypertrophy and dysfunction and from circulatory congestion, only Sx and Dox favorably affected mortality. These findings indicate that in the aortic banding rat model, alpha-adrenoceptors are importantly involved in the pathogenesis of cardiovascular deterioration and disease progression.
Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Hypertension/drug therapy , Hypertrophy, Left Ventricular/prevention & control , Sympathectomy, Chemical , Animals , Aorta, Abdominal/surgery , Blood Pressure , Doxazosin/therapeutic use , Heart Failure/drug therapy , Heart Failure/therapy , Heart Rate , Hypertension/complications , Hypertension/therapy , Hypertrophy, Left Ventricular/etiology , Male , Oxidopamine , Propranolol/therapeutic use , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: High-dose chemotherapy followed by an inoculum of autologous peripheral blood progenitor cells (PBPCs) can improve survival in patients affected with primary systemic amyloidosis (AL). It has been documented, however, that the morbidity and mortality of PBPC mobilization and collection in this setting are higher than in patients with other diseases. To minimize the mobilization and collection-related risks, we developed a multidisciplinary approach involving different specialists to manage AL patients with predominant heart and renal involvement. STUDY DESIGN AND METHODS: We report our experience in 42 patients (23 men, 19 women; median age, 51.2 years; range, 28-68 years) with AL who underwent PBPC mobilization and collection. Twenty of the 42 patients (47.6%) had cardiac involvement and 35 of 42 (83.3%) renal involvement. Thirty-three patients (78.5%) were mobilized with granulocyte-colony-stimulating factor (G-CSF) alone (10 microg/kg) and 9 (21.4%) with cyclophosphamide (CTX) (3 g/m(2)) plus G-CSF (10 microg/kg). RESULTS: The median number of collections per patient after either G-CSF or CTX plus G-CSF was 1.8 (range, 1-3). The median number of CD34+ cells collected in patients mobilized with G-CSF alone was 8.2 x 10(6) per kg (range, 1.35 x 10(6)-21.3 x 10(6)/kg) and in patients mobilized with CTX plus G-CSF it was 8.9 x 10(6) per kg (range, 5.5 x 10(6)-14.9 x 10(6)/kg). Forty of the 42 (95.2%) patients produced the minimum required CD34+ cell target dose (4 x 10(6)/kg). The overall rate of morbidity during the collections was 50 percent (21/42 patients): 18 patients (42.8%) had asymptomatic hypotension, 1 (2.4%) had symptomatic hypotension with nausea and vomiting, and 2 (4.7%) experienced a life-threatening hypotensive episode. There were no procedure-related deaths. CONCLUSION: Our multidisciplinary approach was effective in limiting the serious side effects related to PBPC mobilization and collection in AL patients.