Abstract Introduction We hypothesized that discharged heart failure (HF) patients could develop clinical congestion despite adhering to prescribed diuretics, because ambulation attenuates diuretic ...and natriuretic responsiveness. Methods We studied 9 patients aged 57 ± 13 (mean ± SD) years with New York Heart Association functional class II-III symptoms and ejection fraction <40% (28 ± 7%) and receiving furosemide (≥80 mg/d 113 ± 53 mg/d) plus renin-angiotensin system antagonists and beta-blockade. Inulin and p-amminohippuric acid were infused to estimate glomerular filtration rate (GFR) and renal plasma flow (RPF). Furosemide was administered intravenously at 75% of the usual oral morning dose. Participants were randomized to supine (90 minutes recumbancy) or upright (90 minutes sitting and treadmill walking) posture and assumed the other position on their second day. Primary outcome variables were urine volume and sodium excretion 90 minutes after furosemide. Results On the upright, compared with the supine, day, urine volume (792 ± 484 vs 1,290 ± 503 mL; P = .02) and sodium (79 ± 55 vs 141 ± 61 mmol; P < .01) were attenuated, whereas plasma norepinephrine (4.4 ± 2.7 vs 2.3 ± 1.8 mmol/L; P = .01) and renin (327 ± 250% of supine; P < .01) were augmented. Urinary K+, mean pressure, GFR, and RPF were similar. Conclusions Activation of the sympathetic nervous system and renin-angiotensin axis by upright ambulation may attenuate diuresis and natriuresis by increasing proximal tubular reabsorption of sodium and water.
Background Randomized controlled trials report short- and medium-term outcomes following percutaneous coronary intervention (PCI), but their applicability to the general population is not known. Data ...regarding the long-term clinical outcomes of patients undergoing PCI are lacking. Objective To determine the long-term outcomes of ‘all-comers’ undergoing PCI at a large-volume tertiary cardiac referral centre. Methods A total of 12,662 consecutive patients undergoing an index procedure and entered into the University Health Network's (Toronto, Ontario) prospective registry between April 2000 and September 2007 were identified. In-hospital outcomes were assessed. Follow-up data were obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed to calculate unadjusted survival rates, and Cox multiple regression analysis identified independent predictors of late mortality, major adverse cardiac events and all cardiovascular events. Results The population included a relatively high-risk patient cohort, with 19% older than 75 years of age, 28% with diabetes, 61% with multivessel disease and 1.3% in cardiogenic shock. Urgent procedures comprised 53% of all cases. The all-cause mortality rate at seven years follow-up was 10.6%. Repeat PCI occurred in 14.2% of patients, and coronary artery bypass grafting in 4.2%. Men showed a significant unadjusted survival advantage compared with women. Procedural characteristics such as incomplete revascularization and residual stenosis, in addition to established risk factors, were predictors of poorer long-term outcomes. Cardiogenic shock was the strongest predictor of late mortality. Conclusion In the present large registry of ‘all-comers’ for PCI, long-term major adverse cardiac event rates were low and consistent with outcomes from randomized controlled trials. These data reflect a large cohort in real-world clinical practice, and may help clinicians further characterize and better treat high-risk patients who are undergoing PCI.
Objective To evaluate survival and readmissions to hospital for cardiac events or coronary revascularization (REVASC) in patients having off-pump (OPCAB) versus conventional on-pump (CCAB) coronary ...artery bypass graft surgery (CABG). Methods Of 11,368 consecutive patients undergoing isolated CABG between 1996 and 2002, 514 had OPCAB surgery. Using propensity scores, 503 CCAB patients were randomly matched to 503 OPCAB patients. Results There were no clinical or statistical differences between the two groups for any prognostic variable. However, OPCAB patients received significantly fewer distal anastomoses than the CCAB group (2.6±1.0 versus 3.1±1.0; P<0.001). There was no difference in operative mortality (OPCAB 1.0%, CCAB 1.4%; P=0.6), but the OPCAB group had significantly fewer operative strokes (0.2% versus 1.8%; P=0.01). Follow-up was 99.7% complete at 2.2±1.2 years (range 0 to 6 years). Twice as many OPCAB patients (n=24) required REVASC compared with the CCAB (n=11) group. The following five-year actuarial outcomes are presented for CCAB and OPCAB, respectively: survival: 77±6%, 76±8%, P=0.8; freedom from REVASC: 95±3%, 92±2%, P=0.02; and cardiac event-free survival: 76±5%, 62±8%; P=0.05. Cox regression revealed that OPCAB was a significant independent predictor of poorer freedom from REVASC (RR 2.2, 95% CI 1.0 to 4.6; P=0.04) and cardiac event-free survival (RR 1.6, 95%CI 1.1 to 2.2; P=0.02). Conclusions The use of OPCAB remains controversial. These results, from this early experience, suggest that despite improved hospital outcomes, the lesser degree of REVASC raises concerns about the need for repeat revascularization in the OPCAB group.
The arrhythmogenic substrate in survivors of unexplained cardiac arrest (UCA) has not been defined.
To test the hypothesis that patients with UCA have latent repolarization abnormalities, in ...particular T-wave alternans (TWA), which may be unmasked with epinephrine (EPI) challenge.
We prospectively studied 10 UCA survivors (46 ± 9 years) and 11 first-degree relatives (FDRs) of sudden death victims (37 ± 14 years). Patients with UCA underwent standard clinical testing, which was normal. FDRs had normal clinical history and testing. All subjects underwent an EPI infusion (0.05, 0.1, and 0.2 μg/(kg·min), 5 minutes each dose) while recording continuous digital 12-lead electrocardiograms. Corrected QT interval and QT variability index were evaluated at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose by using the spectral method. Positive (+) TWA at each dose was defined as V(alt) > 0 with k ≥ 3 in 1 or more 128-beat segment in ≥2 electrocardiogram leads. A novel metric, TWA burden, reflecting V(alt) integrated over time (s), was also evaluated for each EPI dose.
There was no difference between UCA survivors and FDRs with respect to heart rate, QT, corrected QT interval, or QT variability index at baseline or during EPI. At baseline, +TWA was similar between UCA survivors and FDRs (10% vs 0%; P = NS). During EPI, +TWA was more prevalent in UCA survivors than in FDRs (80% vs 18%; P = .009). TWA burden was greater in UCA survivors than in FDRs during EPI 0.1 (P = .039) and EPI 0.2 μg/(kg·min) (P = .009).
UCA survivors are more likely to demonstrate latent TWA compared with FDRs, which becomes manifest with EPI. This novel finding provides evidence for an arrhythmogenic substrate in UCA survivors.
Objectives The aim of this study was to compare the survival of patients with hypertrophic cardiomyopathy (HCM) and resting left ventricular outflow tract (LVOT) obstruction managed with an invasive ...versus a conservative strategy. Background In patients with resting obstructive HCM, clinical benefit can be achieved after invasive septal reduction therapy. However, it remains controversial whether invasive treatment improves long-term survival. Methods We studied a consecutive cohort of 649 patients with resting obstructive HCM. Total and HCM-related mortality were compared in 246 patients who were conservatively managed with 403 patients who were invasively managed by surgical myectomy, septal ethanol ablation, or dual-chamber pacing. Results Multivariable analyses (with invasive therapy treated as a time-dependent covariate) showed that an invasive intervention was a significant determinant of overall mortality (hazard ratio: 0.6, 95% confidence interval: 0.4 to 0.97, p = 0.04). Overall survival rates were greater in the invasive (99.2% 1-year, 95.7% 5-year, and 87.8% 10-year survival) than in the conservative (97.3% 1-year, 91.1% 5-year, and 75.8% 10-year survival, p = 0.008) cohort. However, invasive therapy was not found to be a significant independent predictor of HCM-related mortality (hazard ratio: 0.7, 95% confidence interval: 0.4 to 1.3, p = 0.3). The HCM-related survival was 99.5% (1 year), 96.3% (5 years), and 90.2% (10 years) in the invasive cohort, and 97.8% (1 year), 94.6% (5 years), and 86.9% (10 years) in the conservative cohort (p = 0.3). Conclusions Patients treated invasively have an overall survival advantage compared with conservatively treated patients, with the latter group more likely to die from noncardiac causes. The HCM-related mortality is similar, regardless of a conservative versus invasive strategy.
Background Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, ...contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO2 ) in HF relates inversely to MSNA at rest and during exercise. Objective To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO2 ) that is augmented in HF. Methods MSNA at rest and VE/VCO2 during stationary cycling were measured in 30 patients (27 men) with HF (mean ± SD ejection fraction 20 ± 6%) and in 31 age-matched controls (29 men). Results MSNA was higher in HF patients than in controls (51.5 ± 14.3 bursts/min versus 33.0 ± 11.1 bursts/min; P < 0.0001). The VE/VCO2 slope was also higher in HF patients than in controls (33.7 ± 5.7 versus 26.0 ± 3.5; P < 0.0001), whereas pVO2 was lower in HF patients than in controls (18.6 ± 6.6 versus 31.4 ± 8.4 mL/kg/min; P < 0.0001). There were significant relationships between MSNA and VE/VCO2 in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 × MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO2 , identified a significant independent relationship between MSNA burst frequency and VE/VCO2 (P=0.013) that differed between HF and controls (P < 0.01). Conclusions The magnitude of resting sympathetic activity correlates positively with the VE/VCO2 slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.
Sodium restriction is the primary nutritional strategy in heart failure; however, other diet-related concerns may also occur. We characterized dietary intake among stable patients with heart failure ...and a non-heart-failure cardiac control group to quantify and determine prevalence of inadequate micronutrient intake. Two 3-day food records were completed by 123 patients with heart failure and 58 controls. A subset of each group provided two 24-hour urine collections. Mean intake of sodium (2,540±1,122 vs 2,596±1,184 mg/day) and potassium (3,190±980 vs 3,114±828 mg/day) was similar between the heart failure and control groups. Prevalence of inadequate potassium intake was 94% among patients with heart failure and 91% among controls. More than 50% in each group had inadequate intakes of calcium, magnesium, folate, and vitamins D and E. In stable patients with heart failure, sodium intake was not excessive. However, we demonstrated widespread dietary inadequacies of other vitamins and minerals. These findings highlight the importance of diet beyond that of sodium restriction.
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