Prognostic Usefulness of Cardiopulmonary Exercise Testing for Managing Patients With Severe Aortic Stenosis.

The approach to managing asymptomatic or questionably symptomatic patients for aortic stenosis is difficult. We aimed to determine whether cardiopulmonary exercise testing (CPET) is prognostically useful in such patients. Patients judged asymptomatic or questionably symptomatic for aortic stenosis with aortic valve area index <0.6 cm2/m2 and left ventricular ejection fraction ≥0.50 were managed conservatively provided they had either (group 1) normal peak oxygen consumption and peak oxygen pulse (>83% and >95% of the predicted values, respectively) or (group 2) subnormal peak oxygen consumption or peak oxygen pulse but with CPET data pointing to pathologies other than hemodynamic compromise from aortic stenosis. Increase in systolic blood pressure <20 mm Hg, ST depression ≥2 mm, or symptoms during the exercise test were allowed. Unexpected events included cardiac death or hospitalization with heart failure in patients who had not been recommended valve replacement. The median age of the study population (n = 101) was 75 years (interquartile range 65 to 79 years), and 67% were judged questionably symptomatic. During a follow-up at 24 ± 6 months, the rate of unexpected cardiac death and unexpected hospitalization with heart failure was 0% and 6.0%, respectively. All-cause mortality was 4.0% compared with 8.0% in the age- and gender-matched population. For group 1, 26 of 70 (37.1%) succumbed to cardiac death, or were hospitalized because of heart failure, or underwent valve replacement, and for group 2 this was 12 of 31 (38.7%). In conclusion, if CPET does not indicate a significant hemodynamic compromise because of aortic stenosis, an initially conservative strategy results in a good prognosis and an acceptable event rate.

Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site.

AIMS: Previous studies indicate that ventricular pacing may precipitate heart failure (HF). We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome (SSS) randomized to AAIR or DDDR pacing. Furthermore, we investigated effects of percentage of ventricular pacing (%VP) and pacing site in the ventricle. METHODS AND RESULTS: We analysed data from 1415 patients randomized to AAIR (n = 707) or DDDR pacing (n = 708). Ventricular pacing leads were recorded as located in either an apical or a non-apical position. The %VP and HF hospitalizations were recorded during follow-up. Patients were classified with new HF, if in New York Heart Association (NYHA) functional class IV or if presence of ≥2 of: oedema; dyspnoea; NYHA functional class III. Mean follow-up was 5.4 ± 2.4 years. Heart failure hospitalizations did not differ between groups. In the AAIR group, 170 of the 707 (26%) patients developed HF vs. 169 of the 708 (26%) patients in the DDDR group, hazard rate ratio (HR) 1.00, 95% confidence interval (CI) 0.79-1.22, P = 0.87. In DDDR patients, 146 of the 512 patients (29%) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients (17%) with the leads in a non-apical position, HR 0.67, CI 0.45-1.00, P = 0.05. After adjustments this difference was non-significant. The incidence of HF was not associated with %VP (P = 0.57). CONCLUSION: In patients with SSS, HF was not associated with pacing mode, %VP, or ventricular lead localization. This suggests that DDDR pacing is safe in patients with SSS without precipitating HF.

Waiting for a pacemaker: is it dangerous?

AIMS: To determine waiting period-related morbidity, mortality, and adverse events in acute patients waiting for a permanent pacemaker (PPM). METHODS AND RESULTS: A retrospective chart review of all PPM implantations in Region Zealand, Denmark, in 2009 was conducted. Patients were excluded if they were discharged from the hospital during the waiting period or referred from the outpatient department. Adverse events were tracked. Four hundred and eighty-seven PPM implantations were identified. Of these, 259 patients (53.2%) required acute PPM implantation and waited a mean of 5.1 days from PPM indication to implantation. A lack of implantation capacity was responsible for 4.5 of the waiting days. Twenty-nine patients (11.2%) developed infection while waiting, primarily urinary tract infections. Thirteen patients (5.0%) suffered non-sustained ventricular tachycardia, and eight patients (3.1%) suffered clinical cardiac arrest followed by successful resuscitation. Three patients (1.2%) died during the waiting period before successful implantation. Forty-eight patients (18.5%) received the sympathomimetic beta-adrenergic agent, isoprenaline, and seven patients (13.7%) had malignant arrhythmias or cardiac arrest, reaching statistical significance (P < 0.05). Twenty-eight patients (10.8%) had a temporary transvenous-pacing catheter applied acutely. CONCLUSIONS: The patients awaited acute PPM implantations for a mean of 4.5 days because of capacity problems. Overall, 83 patients (32.0%) experienced at least one adverse event during the waiting period. The present study indicates that a waiting period is dangerous as it is associated with an increased risk of adverse events. Acute PPMs should be implanted with a 24-h pacemaker implantation service capacity.

Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing.

AIMS: In the recently published DANPACE trial, incidence of atrial fibrillation (AF) was significantly higher with single-lead atrial (AAIR) pacing than with dual-chamber (DDDR) pacing. The present analysis aimed to evaluate the importance of baseline PQ-interval and percentage of ventricular pacing (VP) on AF. METHODS AND RESULTS: We analysed data on AF during follow-up in 1415 patients included in the DANPACE trial. In a subgroup of 650 patients with DDDR pacemaker, we studied whether %VP, baseline PQ-interval, and programmed atrio-ventricular interval (AVI) was associated with AF burden measured as time in mode-switch (MS) detected by the pacemaker. In the entire DANPACE study population, the incidence of AF was significantly higher in patients with baseline PQ-interval >180 ms (P< 0.001). Among 650 patients with DDDR pacemaker, telemetry data were available for 1.337 ± 786 days, %VP was 66 ± 33%, AF was detected at planned follow-up in 160 patients (24.6%), MS occurred in 422 patients (64.9%), and AF burden was marginally higher with baseline PQ-interval >180 ms (P= 0.028). No significant association was detected between %VP and %MS (Spearman's ρ 0.056, P= 0.154). %MS was not different between minimal-paced programmed AVI ≤ 100 and >100 ms (median value), respectively (P= 0.60). CONCLUSIONS: The present study indicates that a longer baseline PQ-interval is associated with an increased risk of AF in patients with sick sinus syndrome. Atrial fibrillation burden is not associated with the percentage of VP or the length of the programmed AVI.

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome.

AIMS: In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR). METHODS AND RESULTS: We randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n = 707) or DDDR (n = 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6%) died during follow-up vs. 193 patients (27.3%) in the DDDR group, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.88-1.29, P = 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4%) in the AAIR group vs. 163 patients (23.0%) in the DDDR group, HR 1.27, 95% CI 1.03-1.56, P = 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1%) in the AAIR group vs. 84 (11.9%) in the DDDR group (HR 1.99, 95% CI 1.53-2.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups. CONCLUSION: In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158.

Long-term outcome in patients treated with sirolimus-eluting stents in complex coronary artery lesions: 3-year results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) trial.

OBJECTIVES: Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions. BACKGROUND: Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions. METHODS: We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted. RESULTS: At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient. CONCLUSIONS: A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658)

Efficiency and safety of the sirolimus eluting stent in complex coronary artery lesions after cessation of dual antiplatelet therapy: fifteen months clinical outcome of the randomised Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial.

BACKGROUND: The randomised Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial reported considerably less angiographic restenosis after implantation of sirolimus-eluting stents (SES) vs bare metal stents (BMS) in patients with complex coronary lesions. The purpose of this study was to evaluate the clinical outcome after a majority of the SCANDSTENT patients had stopped the dual antiplatelet therapy. METHODS AND RESULTS: The SCANDSTENT trial randomly assigned 322 patients with symptomatic complex coronary artery disease (occlusions, bifurcations, ostial or angulated lesions) to receive SES or BMS. At 15 months after stent implantation, when 80% of the patients had stopped taking clopidogrel, six patients in the SES group and 10 in the BMS group had died or suffered a myocardial infarction (non significant [NS]). Compared with BMS, SES reduced the rate of target vessel revascularisation (TVR) from 33.1% to 5.6% (P<0.001) and the frequency of major adverse cardiac events from 35.7% to 8.6% (p<0.001). Definite stent thrombosis was observed in five patients in the BMS group, and two cases of probable and possible stent thrombosis were observed in the SES group (NS). One case of possible SES thrombosis occurred more than one year after stent implantation. CONCLUSIONS: Compared with BMS, SES markedly reduced the frequency of TVR and MACE within 15 months in SCANDSTENT patients with complex coronary artery lesions without development of delayed restenosis.

Comparison of sirolimus-eluting and bare metal stents in coronary bifurcation lesions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease Trial (SCANDSTENT).

BACKGROUND: Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations. METHODS: SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation. RESULTS: The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02). CONCLUSION: Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

Sirolimus versus bare metal stent implantation in patients with total coronary occlusions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease (SCANDSTENT) trial.

BACKGROUND: Coronary restenosis is more common in a total coronary occlusion (TCO) than other lesion types after implantation of bare metal stents (BMS). But whereas sirolimus-eluting stents (SES) have been shown to improve the outcomes in simple coronary artery lesions, data on their efficacy in complex coronary lesions are scarce. METHODS: We enrolled 127 patients with coronary artery disease and a TCO > or = 15 mm in length to have either SES or BMS implanted after successful recanalization. Outcome measures included the minimal lumen diameter, the late lumen loss, and angiographic restenosis (> 50% diameter stenosis) at 6 months follow-up and the occurrence of target vessel failure during a 7-month period. RESULTS: The patients were well matched in demographic and angiographic baseline characteristics, and 20% had diabetes. The reference vessel was 2.92 mm in mean, and the lesion length was 25.2 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.49 mm compared with 1.46 mm in those who received BMS (P = .015), 0% versus 38% developed restenosis (P < .001), lumen loss was -0.05 versus 0.99 mm (P < .001), and the target vessel failure rate 5% with SES versus 35% with BMS (P < .001). Stent thrombosis occurred in 1 patient in the BMS group. CONCLUSIONS: Implantation of SES is safe, and it markedly reduces angiographic restenosis and the occurrence of adverse events in patients with a TCO.

The Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial.

OBJECTIVES: The purpose of the SCANDSTENT study was to evaluate the use of sirolimus-eluting stents (SES) in complex coronary lesions. BACKGROUND: The use of SES improves angiographic and clinical outcomes compared with bare-metal stents (BMS) in simple coronary artery lesions, but there is limited evidence of their safety and efficacy when implanted in complex lesions. METHODS: We randomly assigned 322 patients with symptomatic complex coronary artery disease to receive either SES or BMS. The lesions were occluded (36%), bifurcational (34%), ostial (22%), or angulated (8%) in morphology. The primary end point was the difference in minimal lumen diameter six months after stent implantation. RESULTS: The patients were well matched in terms of demographic and angiographic baseline characteristics; 18% had diabetes. The reference vessel diameter was 2.86 mm in mean, and the lesion length 18.0 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.48 mm compared with 1.65 mm in those who received BMS (p < 0.001), a diameter stenosis of 19.3% versus 43.8% (p < 0.001), and 2.0% versus 31.9% developed restenosis (p < 0.001). The rate of major adverse cardiac events was 4.3% with SES versus 29.3% with BMS (p < 0.001), and stent thrombosis was observed in 0.6% in the SES group versus 3.1% in the BMS group (p = 0.15). CONCLUSIONS: The use of SES markedly reduced restenosis and the occurrence of major adverse cardiac events in patients with complex coronary artery lesions without increasing the risk of stent thrombosis.

Low restenosis rate of the NIR coronary stent: results of the Danish multicenter stent study (DANSTENT)--a randomized trial comparing a first-generation stent with a second-generation stent.

BACKGROUND: Larger studies evaluating the angiographic results of second-generation stents are scarce. The objectives of this study were to assess current standards of angiographic and clinical outcomes after implantation of the second-generation stainless steel stent, NIR (Medinol Ltd, Tel Aviv, Israel), and to compare the outcomes with those of the first-generation Palmaz-Schatz (PS) stent (Johnson & Johnson, Warren, NJ). METHODS: Patients having coronary artery lesions that could be covered by a stent of 15 mm in length were randomly assigned to receive the NIR or the PS. Procedural success, 6-month angiographic findings, and 1-year clinical outcomes were determined. RESULTS: In 424 patients included in the study, the overall procedural success rate was high (NIR 98%, PS 99%, P =.90). Follow-up angiography was conducted in 91% of the patients. The overall rate of angiographic restenosis was low in both groups (NIR 9.9%, PS 12.6%, P =.35). We found a low restenosis rate in vessels with a minimal lumen diameter >3.1 mm after the procedure, particularly in the NIR group (<6%). The rate of target lesion revascularization after 1 year did not differ (NIR 12%, PS 10%, P =.47). CONCLUSIONS: The angiographic and clinical outcomes after implantation of the second-generation stainless steel stent were not significantly better than those of the first-generation stent. The low restenosis rates, particularly in patients with the largest minimal lumen diameters after stent implantation, warrants circumspection when planning the evaluation of newer stent technologies that aim to further reduce coronary restenosis.

Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.

BACKGROUND: Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. METHODS: The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. RESULTS: The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). CONCLUSIONS: A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.