Danish health authorities have major concerns with regard to the risk and the quality of care of percutaneous coronary intervention (PCI) without onsite cardiac surgery. We report the results of the first Danish PCI centre without onsite cardiac surgery.A total of 245 patients underwent 254 elective PCIs during a six-month study period. The outcome measures were treatment latency, health care costs, mortality rate, major adverse cardiovascular events, symptom relief and quality-of-life at six-month follow-up.The median treatment latency was reduced from 28 to no days (p < 0.05) for patients with stable disease, and from seven to no days (p < 0.05) for patients with unstable disease. Health care costs were reduced by 4,246,652 DKK. The six-month mortality was 0.0% versus a predicted 0.4% New York State PCI-score in patients with stable disease, and a 1.4% observed study score versus a predicted 6.4% GRACE-score in patients with unstable disease. No patients required emergency bypass surgery. At six months, five myocardial infarctions (two periprocedural and two subacute stent thromboses), three restenoses and no in-stent restenosis had occurred, while angina was absent or reduced in 92% and quality-of-life had improved in 73% of the patients.Local PCI without onsite cardiac surgery was safe, quality of care was increased, health care costs were reduced and patient-perceived treatment effect was excellent.
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.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.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).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.
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. 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. For patients who are asymptomatic or questionably symptomatic for aortic stenosis, it is often difficult to determine whether or not the patient has significant hemodynamic compromise resulting from the aortic stenosis. In particular, this diagnosis is difficult for patients aged >70 years, for those who are classified as functional class II, and for patients with co-morbidities or a sedentary lifestyle.1Das P. Rimington H. Chambers J. Exercise testing to stratify risk in aortic stenosis.Eur Heart J. 2005; 26: 1309-1313Crossref PubMed Scopus (286) Google Scholar, 2Bonow R.O. Exercise hemodynamics and risk assessment in asymptomatic aortic stenosis.Circulation. 2012; 126: 803-805Crossref PubMed Scopus (10) Google Scholar Field exercise testing is often used,3Vahanian A. Alfieri O. Andreotti F. Antunes M.J. Baron-Esquivias G. Baumgartner H. Borger M.A. Carrel T.P. DeBonis M. Evangelista A. Falk V. Iung B. Lancellotti P. Pierard L. Price S. Schafers H.J. Schuler G. Stepinska J. Swedberg K. Takkenberg J. von Oppell U.O. Windecker S. Zamorano J.L. Zembala M. Guidelines on the management of valvular heart disease.Eur Heart J. 2012; 33: 2451-2496Crossref PubMed Scopus (3188) Google Scholar but this is of limited value in such patients.1Das P. Rimington H. Chambers J. Exercise testing to stratify risk in aortic stenosis.Eur Heart J. 2005; 26: 1309-1313Crossref PubMed Scopus (286) Google Scholar, 2Bonow R.O. Exercise hemodynamics and risk assessment in asymptomatic aortic stenosis.Circulation. 2012; 126: 803-805Crossref PubMed Scopus (10) Google Scholar In contrast to field exercise testing, cardiopulmonary exercise testing (CPET) is a laboratory test that assays cardiopulmonary physiology during exercise in greater detail.4Wasserman K. Diagnosing cardiovascular and lung pathophysiology from exercise gas exchange.Chest. 1997; 112: 1091-1101Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar Aortic valve replacement (AVR) is not without risks or complications,5Danish Heart Registry Yearly report.http://www.si-folkesundhed.dk/upload/dhr_%C3%A5rsberetning_2012.pdfDate: 2012Google Scholar and patients are often reluctant to undergo this operation, causing them to postpone AVR. It is valuable for physicians and patients to possess knowledge about which parameters predict a safe initial deferral. We hypothesized that for patients judged to be asymptomatic or equivocally or mildly symptomatic for severe aortic stenosis by a cardiologist, an initial conservative treatment strategy could yield a good prognosis and acceptable event-rate after stratification by a CPET. This includes patients aged >70 years, with New York Heart Association II classification or an abnormal field exercise test. Our primary aim was to demonstrate that if peak oxygen consumption (VO2) and peak oxygen pulse (O2pulse) were either (1) not subnormal or (2) subnormal, but CPET results pointed to major causes other than hemodynamic compromise from the aortic stenosis, the following end points would occur with a low and acceptable incidence.A.Unexpected cardiac death or hospitalization with heart failure. Defined as a cardiac death or hospitalization with heart failure in a patient that had not been recommended AVR earlier in the study period.B.Cardiac death, hospitalization with heart failure, or progression to AVR.C.All-cause mortality. All-cause mortality was compared with the age- and gender-matched mortality in our region (similar distribution of gender and age groups in 5-year intervals), which can be calculated from Reference 6Statistics Denmark Death by region, age and sex.http://www.statbank.dk/FOD507Google Scholar. Patients were recruited from our outpatient clinic. Inclusion criteria were as follows: asymptomatic, equivocally, or mildly symptomatic status from aortic stenosis as judged by a cardiologist, aortic valve area index <0.6 cm2/m2, and left ventricular ejection fraction ≥0.50. Exclusion criteria were as follows: more than trivial other valvular disease, atrial fibrillation with a resting heart rate >90 beats/min, inability to perform bicycle exercise test, and other known medical conditions or abuse that could result in survival rate <2 years. All included patients provided written informed consent, and the study was approved by the local ethics committee (1-01-83-0002-07). Based on the outcomes and evaluations of the baseline CPET, the patients were prospectively categorized. Patients in whom peak VO2 and peak O2pulse were either not subnormal (group 1) or subnormal, but CPET results pointed to major causes other than hemodynamic compromise from aortic stenosis (group2), followed an initial conservative strategy. Predefined criteria for group 1 and group 2 are presented under Table 1. Patients with subnormal peak VO2 and peak O2pulse not explainable by causes other than hemodynamic compromise from aortic stenosis were referred for AVR. These patients were not included in the present study.Table 1Baseline characteristics in the two groupsGroup 1Group 2(n = 70)(n = 31)Age (years)73 ± 1072 ± 7Male/female (n)38/3223/8Hypertension36 (52%)25 (80%)*Diabetes mellitus9 (13%)3 (10%)Prior ischemic heart disease3 (4%)6 (19%)Chronic obstructive lung disease4 (6%)13 (42%)†Smoker9 (13%)9 (29%)Atrial fibrillation2 (3%)9 (29%)†Pacemaker2 (3%)1 (3%)NYHA class ≥ II24 (34%)21 (68%)*Equivocally/mildly symptomatic41 (59%)26 (84%)*Body mass index (kg/m2)27 ± 428 ± 5Body surface area m21.9 ± 0.22.0 ± 0.2Creatinine (µmol/L)80 ± 2088 ± 23LDL-cholesterol (mmol/L)3.1 ± 1.02.8 ± 0.9LDL-cholesterol (mg/dl)120 ± 39108 ± 35Hemoglobin (mmol/L)8.8 ± 0.68.7 ± 0.9Brain natriuretic peptide > upper level of normal11 (17%)12 (39%)Resting systolic blood pressure (mm Hg)133 ± 14133 ± 19EchocardiographyAortic valve area index (cm2/m2)0.43 ± 0.090.46 ± 0.08Mean gradient (mm Hg)42 ± 1533 ± 11*Left ventricular ejection fraction59 ± 457 ± 5Sa (cm/s)5.1 ± 1.24.9 ± 1.2E/e′13.5 ± 5.013.7 ± 5.3Left ventricular posterior wall thickness (cm)1.13 ± 0.221.16 ± 0.30Cardiovascular drugsBeta blockers14 (20%)15 (48%)*Digoxin3 (4%)2 (7%)Calcium-blockers23 (33%)5 (16%)ACE-/AT-II-inhibitors22 (31%)17 (55%)Diuretics27 (39%)11 (36%)Statins40 (57%)19 (61%)Data are presented as mean ± SD or n (frequency %). * p < 0.01 and † p < 0.001 compared with Group 1. Measurement of brain natriuretic peptide was not obtained in 3 and 1 patients in Group 1 and 2, respectively. NYHA = New York Heart Association. Sa = Peak systolic velocity (Color tissue Doppler). E/e′ = Peak early mitral inflow velocity/early diastolic mitral annulus velocity (Pulsed tissue Doppler).Group 1. Normal CPX results. Peak VO2 ≥ 83% of that predicted and peak O2pulse ≥95% of that predicted.Group 2. Abnormal CPX results judged not likely caused by aortic stenosis. 1) Peak VO2 < 83% of that predicted and one of the following: a) normal peak O2pulse defined as >95% of that predicted, b) low effort (respiratory coefficient <1), c) pulmonary disease with forced expiratory volume in first second to forced vital capacity ratio < 70% of that predicted, low breathing reserve, high VE/VCO2, and normal O2pulse trajectory—or 2) Peak VO2 ≥ 83% and peak O2pulse < 95% of that predicted. Open table in a new tab Data are presented as mean ± SD or n (frequency %). * p < 0.01 and † p < 0.001 compared with Group 1. Measurement of brain natriuretic peptide was not obtained in 3 and 1 patients in Group 1 and 2, respectively. NYHA = New York Heart Association. Sa = Peak systolic velocity (Color tissue Doppler). E/e′ = Peak early mitral inflow velocity/early diastolic mitral annulus velocity (Pulsed tissue Doppler). Group 1. Normal CPX results. Peak VO2 ≥ 83% of that predicted and peak O2pulse ≥95% of that predicted. Group 2. Abnormal CPX results judged not likely caused by aortic stenosis. 1) Peak VO2 < 83% of that predicted and one of the following: a) normal peak O2pulse defined as >95% of that predicted, b) low effort (respiratory coefficient <1), c) pulmonary disease with forced expiratory volume in first second to forced vital capacity ratio < 70% of that predicted, low breathing reserve, high VE/VCO2, and normal O2pulse trajectory—or 2) Peak VO2 ≥ 83% and peak O2pulse < 95% of that predicted. The study patients were followed with clinical evaluations at 3 months' intervals. Echocardiography and CPET were performed at 6 and 12 months' intervals, respectively. If a patient presented new or worsening symptoms, or if he or she described decreasing functional capacity, a CPET and an echocardiogram were recommended. The patient was also referred for a coronary angiogram, and a decision regarding AVR was made by an independent Heart Team (nonstudy physicians), who did not possess knowledge of the details of the CPET. Nine months post-AVR an echocardiography and a CPET were recommended. Vital status, hospitalizations, and AVR data were obtained on December 1, 2012 from the Danish National Patient Registry, hospital records, and information obtained during the study. The cause of death was determined from the primary diagnosis in the discharge summary. CPET was performed on a bicycle ergometer with breath-by-breath measurement of the VO2, carbon dioxide exhaustion (VCO2), and minute ventilation (VE) (Innocor, Innovision version 6.15, Odense, Denmark) as previously described.7Van Le D. Jensen G.V.J. Carstensen S. Kjøller-Hansen L. Cardiopulmonary exercise testing in asymptomatic or equivocal symptomatic aortic stenosis. Feasibility, reproducibility, safety and information obtained on exercise physiology.Cardiology. 2016; 133: 147-156Crossref PubMed Scopus (12) Google Scholar The key measurements obtained from CPET were peak VO2 (expressing cardiac output), peak O2pulse (expressing stroke volume), VE/VCO2 at nadir (a higher value indicates a ventilatory/flow mismatch), and the respiratory coefficient (R = VCO2/VO2, where a value at peak exercise <1 points to inadequate effort or nonphysiological hyperventilation). An estimate of stroke volume (milliliter) at peak exercise was obtained from the following calculation (peak O2pulse/hemoglobin in g/dL) × 100; O2pulse/hemoglobin index). This was because hemoglobin in gram per deciliter corresponds to the milliliter of oxygen extraction per deciliter.8Agostoni P.G. Wasserman K. Perego G.B. Guazzi M. Cattadori G. Palermo P. Lauri G. Marenzi G. Non-invasive measurement of stroke volume during exercise in heart failure patients.Clin Sci. 2000; 98: 545-551Crossref PubMed Google Scholar, 9Wasserman K. Hansen E.J. Sue Y.D. Stringer W.W. Whipp B.J. Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications.4th ed. Lippincott, Williams and Wilkins, Philadelphia, PA2005Google Scholar The predicted peak VO2 was defined according to current recommendations.10Guazzi M. Adams V. Conraads V. Halle M. Mezzani A. Vanhess L. Arena R. Fletcher G.F. Forman D.E. Kitzman D.W. Lawie C.J. Myers J. European Association for Cardiovascular Prevention & Rehabilitation; American Heart Association. EACPR/AHA Scientific Statement Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations.Circulation. 2012; 126: 2261-2274Crossref PubMed Scopus (471) Google Scholar A peak VO2 <83% of the predicted value, which represents the lower 95% confidence value in a healthy sedentary population,9Wasserman K. Hansen E.J. Sue Y.D. Stringer W.W. Whipp B.J. Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications.4th ed. Lippincott, Williams and Wilkins, Philadelphia, PA2005Google Scholar, 11Sue D.Y. Hansen J.E. Normal values in adults during exercise testing.Clin Chest Med. 1984; 5: 89-98Abstract Full Text PDF PubMed Google Scholar was regarded as abnormal. The predicted peak heart rate was calculated as 220 minus the patient's age. The predicted peak O2 pulse was calculated as the predicted peak VO2/predicted peak heart rate.9Wasserman K. Hansen E.J. Sue Y.D. Stringer W.W. Whipp B.J. Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications.4th ed. Lippincott, Williams and Wilkins, Philadelphia, PA2005Google Scholar A peak O2 pulse of <95% of the expected was regarded as abnormal.7Van Le D. Jensen G.V.J. Carstensen S. Kjøller-Hansen L. Cardiopulmonary exercise testing in asymptomatic or equivocal symptomatic aortic stenosis. Feasibility, reproducibility, safety and information obtained on exercise physiology.Cardiology. 2016; 133: 147-156Crossref PubMed Scopus (12) Google Scholar An inert gas breathing test was performed as previously described.7Van Le D. Jensen G.V.J. Carstensen S. Kjøller-Hansen L. Cardiopulmonary exercise testing in asymptomatic or equivocal symptomatic aortic stenosis. Feasibility, reproducibility, safety and information obtained on exercise physiology.Cardiology. 2016; 133: 147-156Crossref PubMed Scopus (12) Google Scholar All patients underwent 2-dimensional and Doppler echocardiography as previously described.7Van Le D. Jensen G.V.J. Carstensen S. Kjøller-Hansen L. Cardiopulmonary exercise testing in asymptomatic or equivocal symptomatic aortic stenosis. Feasibility, reproducibility, safety and information obtained on exercise physiology.Cardiology. 2016; 133: 147-156Crossref PubMed Scopus (12) Google Scholar Lateral E/e′ was calculated as an expression of diastolic pressure. Left ventricular systolic function was assessed using the peak systolic tissue velocity (Sa) obtained by color tissue Doppler.12Bruch C. Stypmann J. Grude M. Gradaus R. Breithardt G. Wichter T. Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy.Am Heart J. 2004; 148: 696-702Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar The mean of the septal and lateral Sa values was used. For economic and logistical reasons, different assays for brain natriuretic peptide were used during the study period. Therefore, we present data for the plasma brain natriuretic peptide levels according to the upper level of normal, incorporating age and gender. The most frequently used assay had upper levels of normal ranging from 25 pg/ml (youngest man) to 77 pg/ml (oldest woman). For statistical calculations, SPSS Statistics software version 20 (IBM Corp., Armonk, New York) was used. Continuous variables are presented as their means ± SD if not otherwise indicated. Unpaired t tests and 95% confidence intervals (CI) were used to compare the means of 2 groups. Paired t tests were used to determine serial changes. To calculate between-group differences in categorical variables, Fisher's test was used. The 95% CI for proportions were calculated according to Newcombe.13Newcombe R.G. Two-sided confidence intervals for the single proportion: comparison of seven methods.Stat Med. 1998; 17: 857-872Crossref PubMed Scopus (3033) Google Scholar The normality of the continuous variables was secured with a Shapiro-Wilk test. Over the course of 19 months (March 1 2010 to October 1 2011), 119 patients fulfilled the study criteria and consented. Eighteen patients were immediately recommended AVR because CPET suggested a significant hemodynamic compromise, likely resulting from the aortic stenosis. These patients were excluded from this study. Data for these 18 patients are presented in the supplemental material (Table S1, Table S2). Baseline characteristics and baseline CPET results for the study population (n = 101) are presented in Table 1 and Table 2, respectively. The median age in the study population was 75 years (interquartile range 65 to 79 years). The clinical outcomes over a mean observation time of 24 months (ranging from 12 to 36 months) with complete follow-up are presented in Table 3. The impact of possible predictors on outcomes is presented in Table 4 and in the supplemental material (Table S3).Table 2Cardiopulmonary exercise test results in the two groupsGroup 1(n = 70)Group 2(n = 31)Peak VO2 (mL/min/kg)22.0 ± 6.016.5 ± 3.7†Peak VO2 (% of predicted)110 ± 1878 ± 12†Peak O2pulse (mL O2 per beat)12.7 ± 3.311.0 ± 3.0Peak O2pulse (% of predicted)120 ± 1994 ± 21†% of predicted peak heart rate89 ± 1183 ± 14Respiratory coefficient1.07 ± 0.101.03 ± 0.09Anaerobic threshold (at % of predicted peak VO2)71 ± 1451 ± 9†VE/VCO230 ± 333 ± 6*% of predicted forced expiratory volume first second103 ± 3084 ± 25†Breathing Reserve43 ± 2045 ± 21Stroke volume index resting (mL/m2)34 ± 929 ± 8*Stroke volume index submaximal exercise (mL/m2)43 ± 936 ± 9*PeakO2pulse/Hemoglobin index (mL/m2)47 ± 840 ± 9†Systolic blood pressure increase < 20 mm Hg21 (30%)8 (26%)Symptoms during exercise test3 (4%)9 (29%)†Valvuloarterial impedance5.5 ± 1.76.1 ± 1.5Data are presented as mean ± SD or n (%). * p < 0.01, † p < 0.001 compared with Group 1.VO2 = Oxygen consumption; O2pulse = Oxygen pulse (VO2/heart rate); VE/VCO2 = Ventilation/Carbon dioxide exhaustion at nadir; Valvuloarterial impedance = (Systolic blood pressure + mean gradient)/Stroke volume index at rest. Stroke volume index measured by inert gas rebreathing. Open table in a new tab Table 3Clinical outcomeAll study patients(n = 101)Group 1(n = 70)Group 2(n = 31)Unexpected cardiac death000Unexpected hospitalization with heart failure6 (6%)6 (9%)0Cardiac death, hospitalization with heart failure or aortic valve replacement38 (38%)26 (37%)12 (39%)Deaths of all causes4 (4%)1 (1.4%)3 (10%)Cardiac death1 (1%)01 (3%)Hospitalization with heart failure8 (8%)6 (9%)2 (7%)Cardiac death or hospitalization with heart failure8 (8%)6 (9%)2 (7%)Aortic valve replacement36 (36%)25 (36%)11 (36%)Data are presented as n (%).Unexpected events: Events in patients not recommended aortic valve replacement earlier during the study. There were no sudden deaths. Open table in a new tab Table 4Odds ratios for possible predictors of outcomeCardiac death or Hospitalized with heart failureOdds ratio(95% confidence interval)Cardiac deathHospitalized with heart failure or aortic valve replacementOdds ratio(95% confidence interval)Equivocally/mildly symptomatic0.5 (0.1–2.0)1.0 (0.4–2.3)NYHA class II or III0.73 (0.2–3.2)0.4 (0.2–1.0)*P = 0.04 for worse outcome in NYHA class I.Brain natriuretic peptide > ULN3.5 (0.8–15)1.8 (0.7–4.7)Symptoms during exercise test-†No patients with symptoms or ST-depression during exercise test suffered cardiac death or hospitalization with heart failure.0.5 (0.1–2.0)Increase in SBP < 20 mm Hg0.8 (0.2–4.3)1.0 (0.4–2.5)ST-depression ≥ 2 mm-†No patients with symptoms or ST-depression during exercise test suffered cardiac death or hospitalization with heart failure.0.91 (0.4–2.3)Respiratory coefficient < 10.5 (0.1-4-0)0.7 (0.2–2.0)ULN = Upper level of normal according to age and gender; SBP = Systolic blood pressure.* P = 0.04 for worse outcome in NYHA class I.† No patients with symptoms or ST-depression during exercise test suffered cardiac death or hospitalization with heart failure. Open table in a new tab Data are presented as mean ± SD or n (%). * p < 0.01, † p < 0.001 compared with Group 1. VO2 = Oxygen consumption; O2pulse = Oxygen pulse (VO2/heart rate); VE/VCO2 = Ventilation/Carbon dioxide exhaustion at nadir; Valvuloarterial impedance = (Systolic blood pressure + mean gradient)/Stroke volume index at rest. Stroke volume index measured by inert gas rebreathing. Data are presented as n (%). Unexpected events: Events in patients not recommended aortic valve replacement earlier during the study. There were no sudden deaths. ULN = Upper level of normal according to age and gender; SBP = Systolic blood pressure. One patient succumbed to cardiac death from progressive heart failure 17 months after the baseline CPET, but this patient had been recommended AVR for the first time 8 months earlier and again 4 months earlier during hospitalization with heart failure. Among the patients who were hospitalized for heart failure, 2 (both from group 2) had been recommended for AVR earlier during the study. However, both patients had declined the operation. In group 1, hospitalizations with heart failure were triggered by new dysregulated atrial fibrillation in 2 patients and by an anterior ST elevation myocardial infarction in 1 other patient. The all-cause mortality of 4.0% (95% CI 1.6% to 9.7%) at a mean 2-year follow-up was not higher than that of the age- and gender-matched population in our region. This was 4.0% per year,5Danish Heart Registry Yearly report.http://www.si-folkesundhed.dk/upload/dhr_%C3%A5rsberetning_2012.pdfDate: 2012Google Scholar amounting to 8% over 2 years. A table describing the age and gender distributions of the study population is provided in the supplemental material (Table S4). Causes of death included progressive heart failure (n = 1), ileus (n = 1), pancreatitis secondary to gallstones (n = 1), and alcoholic hepatitis (n = 1). The 30-day and 1-year mortality rates among the 582 non–high-risk patients who underwent single AVR in our country and were reported to the Danish Heart Register in 2012 were 1.5% and 5.3%, respectively.5Danish Heart Registry Yearly report.http://www.si-folkesundhed.dk/upload/dhr_%C3%A5rsberetning_2012.pdfDate: 2012Google Scholar The mean time interval from baseline CPET to clinical progression leading to AVR was 18 ± 6 and 14 ± 7 months in groups 1 and 2, respectively. AVR was performed at a mean of 2.0 ± 1.5 months thereafter. The clinical progression leading to AVR included the following: hospitalization with heart failure (n = 6), new or progressing exercise-induced symptoms (dyspnea or syncope) or decreasing threshold for symptoms (n = 25), new atrial fibrillation and progression in dyspnea (n = 2), angina pectoris or acute coronary syndrome (n = 2), and progressive worsening of CPET results in an asymptomatic patient with very severe aortic stenosis (n = 1). Surgical AVR, surgical AVR with coronary artery bypass, and transfemoral AVR were performed in 21, 11, and 4 patients, respectively. Transfemoral AVR was not performed for clinical reasons, but as part of a randomized study of patients older than 70 years eligible for surgical AVR that showed neutral outcome.14Thyregod H.C.H. Steinbrüchel D.A. Ihlemann N. Nissen H. Kjeldsen B.J. Peursson P. Chang Y. Franzen O.F. Engstrøm T. Clemmensen P. Hansen P.B. Andersen L.W. Olsen P.S. Søndergaard L. Transcatheter versus surgical valve replacement in patients with severe aortic valve stenosis.J Am Coll Cardiol. 2015; 65: 2184-2194Abstract Full Text Full Text PDF PubMed Scopus (675) Google Scholar Serial measurements of peak VO2 at baseline, pre-AVR ("symptomatic state"), and 9 months post-AVR were available for 23 of 25 patients in group 1 and for 9 of 11 patients in group 2 (Figure 1). Serial echocardiographic data were available in 22 of 25 patients and 8 of 11 patients in groups 1 and 2, respectively: From immediately preoperatively (symptomatic state) to 9 months postoperatively, Sa increased from 4.8 ± 1.1 cm/s to 5.5 ± 1.4 cm/s (95% CI for an increase 0.22 to 1.12 cm/s, p = 0.006) in group 1 and from 4.2 ± 1.2 cm/s to 5.1 ± 0.74 cm/s (95% CI for an increase −0.34 to 2.01 cm/s, p = 0.13) in group 2. The E/e′ decreased from 17.6 ± 7.0 to 13.3 ± 5.4 (95% CI for a decrease −7.3 to −1.4 cm/s, p = 0.006) in group 1 and 14.4 ± 5.3 to 13.6 ± 5.3 (95% CI for a decrease −5.87 to 4.13 cm/s, p = 0.68) in group 2. Among the patients who had AVR and a plasma brain natriuretic peptide measurement obtained at baseline and post-AVR, the number of patients with a value greater than the upper level of normal was 11 of 32 at baseline and 13 of 32 post-AVR. According to our predefined criteria, we found that if CPET did not indicate significant hemodynamic compromise resulting from aortic stenosis, an initially conservative treatment strategy had a good prognosis for subsequent years with no unexpected cardiac deaths. Patient survival rate was comparable with the age- and gender-matched population, and only 35% of patients required an AVR during a mean follow-up period of 2 years. A normal CPET (group 1) did not prevent unexpected hospitalization with heart failure, and the rate of hospitalization with heart failure or AVR was similar to group 2. Obviously, a peak VO2 of 90% of the predicted is abnormal if the patient's normal peak VO2 was 120%. However, we do not think that a patient with such a decrease would be regarded as asymptomatic or questionably symptomatic by a cardiologist. Thus, they would not represent the typical patient included in our study. Mortality was low in group 1, which is unsurprising because of the close relation between peak VO2 and survival. Significant improvements in peak VO2 after AVR were observed, suggesting the valve disease was a major cause of symptoms in those who progressed to AVR in this group. Patients in group 2 had subnormal values of peak VO2 and/or peak O2pulse. Thus, they displayed objectively decreased exercise capacity. Furthermore, 84% had some symptoms in daily life, and 68% were deemed New York Heart Association functional class II. Therefore, a physician could have referred nearly all of these patients for AVR because of severe aortic stenosis and symptoms or decreased exercise capacity. Nevertheless, the rate of unexpected cardiac death or hospitalization with heart failure was 0% in group 2. For patients in group 2 who had an AVR, improvements in peak VO2 were not observed. Because Sa and E/e′ tended to improve, this suggest that the timing of AVR was not overdue. The low peak VO2 and lack of improvements in peak VO2 suggest that causes other than the valve disease were the major reasons for symptoms and low functional capacity. The mean gradient was low compared with the aortic valve area index, although the mean Sa and left ventricular ejection fraction values were comparable with those in group 1. This is well explained by the resting stroke volume that was clearly lower, as assessed by inert gas rebreathing (Table 1). A lower resting stroke volume is a key finding in unfit subjects with normal left ventricular ejection fraction.15Saltin B. Calbet J.A. In health and in a normoxic environment, VO2 max is limited primarily by cardiac output and locomotor muscle blood flow.J Appl Physiol. 2006; 100: 744-748Crossref PubMed Scopus (161) Google Scholar The mortality in this group was 9.9%. Although there is uncertainty because of the low n, this is acceptable compared with the expected 8% in the age- and gender-matched population because of the high rate of co-morbidities. How does this study expand upon previous studies? Das et al1Das P. Rimington H. Chambers J. Exercise testing to stratify risk in aortic stenosis.Eur Heart J. 2005; 26: 1309-1313Crossref PubMed Scopus (286) Google Scholar found that field exercise testing was not useful in patients >70 years or in those deemed functional class II. Patients with co-morbidities,1Das P. Rimington H. Chambers J. Exercise testing to stratify risk in aortic stenosis.Eur Heart J. 2005; 26: 1309-1313Crossref PubMed Scopus (286) Google Scholar, 16Marechaux S. Hachicha Z. Bellouin A. Dumesnil J.G. Meimoun P. Pasquet A. Bergeron S. Arsenault A. Tourneau T.L. Ennezat P.V. Pibarot P. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis.Eur Heart J. 2010; 31: 1390-1397Crossref PubMed Scopus (204) Google Scholar symptoms during the test16Marechaux S. Hachicha Z. Bellouin A. Dumesnil J.G. Meimoun P. Pasquet A. Bergeron S. Arsenault A. Tourneau T.L. Ennezat P.V. Pibarot P. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis.Eur Heart J. 2010; 31: 1390-1397Crossref PubMed Scopus (204) Google Scholar, 17Lancellotti P. Magne J. Donal E. O'Connor K. Dulgheru R. Rosca M. Pierard L.A. Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis.Circulation. 2012; 126: 851-859Crossref PubMed Scopus (136) Google Scholar—a subjective criterion,2Bonow R.O. Exercise hemodynamics and risk assessment in asymptomatic aortic stenosis.Circulation. 2012; 126: 803-805Crossref PubMed Scopus (10) Google Scholar or a low exercise capacity17Lancellotti P. Magne J. Donal E. O'Connor K. Dulgheru R. Rosca M. Pierard L.A. Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis.Circulation. 2012; 126: 851-859Crossref PubMed Scopus (136) Google Scholar were excluded in many studies. However, patients with aortic stenosis are often older. They also tend to have co-morbidities and symptoms that are difficult to assess. It is for these patients that decisions regarding treatment strategies are difficult and ambiguous. Our study suggests that CPET is useful in such patient groups. This included patients with revealed symptoms, ST depression >2 mm, decreased blood pressure response during exercise test, low exercise capacity, respiratory coefficient <1, or brain natriuretic peptide greater than the upper level of normal. In a cohort with a mean age of 64 years and 53% (n = 71) with an aortic valve area <1 cm2/m2, Marechaux et al16Marechaux S. Hachicha Z. Bellouin A. Dumesnil J.G. Meimoun P. Pasquet A. Bergeron S. Arsenault A. Tourneau T.L. Ennezat P.V. Pibarot P. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis.Eur Heart J. 2010; 31: 1390-1397Crossref PubMed Scopus (204) Google Scholar found an event rate of cardiac death, heart failure, or AVR of 50% after a mean follow-up of 20 months after a normal field exercise test result, that is, a negative predictive value of 50%. In the older population in our study, all of them had an aortic valve area index <0.6 cm2/m2, and the event rate at a mean follow-up of 24 months was 37%. This presents a negative predictive value for a CPET without suggesting a significant hemodynamic compromise of 63%. In a meta-analysis that included 491 largely asymptomatic patients with a mean age of 62 years and a mean aortic valve area index of 0.47 cm2/m2, the rate of cardiac death or symptoms leading to AVR was 42% at a mean follow-up of 14 months.18Rafique A.M. Biner S. Ray I. Forrester J.S. Tolstrup K. Siegel R.J. Meta-analysis of prognostic value of stress testing in patients with asymptomatic severe aortic stenosis.Am J Cardiol. 2009; 104: 972-977Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar These observations suggest that a CPET-guided strategy may lead to a lower event rate (higher negative predictive value) than that obtained using a field exercise test strategy without sacrificing safety. Our study had some limitations. Only a few patients in our cohort (9%) had very severe aortic stenosis with peak gradients >100 mm Hg.7Van Le D. Jensen G.V.J. Carstensen S. Kjøller-Hansen L. Cardiopulmonary exercise testing in asymptomatic or equivocal symptomatic aortic stenosis. Feasibility, reproducibility, safety and information obtained on exercise physiology.Cardiology. 2016; 133: 147-156Crossref PubMed Scopus (12) Google Scholar However, only in cases when the cardiologist judges the patient asymptomatic or equivocally symptomatic for severe or borderline to severe aortic stenosis is assessment ambiguous, requiring additional diagnostic information. Furthermore, patients who were not able to perform an exercise test were not referred or included. However, such frail patients are seldom considered for AVR if they are only asymptomatic or questionably symptomatic. No randomization against field exercise testing was done. However, the limitations of field exercise testing in patients aged >70 years with co-morbidities or with some symptoms or functional limitation are well-recognized.1Das P. Rimington H. Chambers J. Exercise testing to stratify risk in aortic stenosis.Eur Heart J. 2005; 26: 1309-1313Crossref PubMed Scopus (286) Google Scholar Therefore, we feel that our finding that a CPET-guided strategy was followed by a good prognosis and an acceptable event rate, in such patients who are difficult to assess, provides new and useful information. To compare mortality with that in the background population would ideally also demand a match in peak VO2, because some patients can be supervariants with aortic stenosis. Obviously, this is a nearly impossible task. The cause of death and hospitalizations for heart failure was not determined by an independent assessment committee. However, all deaths occurred in the hospital at other institutions, and the cause of death was determined by local physicians and stated in the discharge summary. In conclusion, we examined a study population with a median age of 75 years that displayed echocardiographically severe aortic stenosis, including two-thirds who had some symptoms. If CPET did not indicate primary significant hemodynamic compromise from the aortic stenosis, we found that an initially conservative treatment strategy was associated with a good prognosis and an acceptable rate of cardiac events. The authors have no conflicts of interest to disclose. The following is the supplementary data to this article: Download .docx (.02 MB) Help with docx files Table S1Baseline variables for those referred for Heart Team evaluation for aortic valve replacement at baseline. Abnormal cardiopulmonary exercise test result judged caused by aortic stenosis. Download .docx (.01 MB) Help with docx files Table S2Baseline cardiopulmonary exercise test result variables for those referred for Heart Team evaluation for aortic valve replacement at baseline. Abnormal cardiopulmonary exercise test judged caused by aortic stenosis. Download .docx (.02 MB) Help with docx files Table S3Impact of possible predictors on outcome. Download .docx (.01 MB) Help with docx files Table S4Distribution of study population according to age and gender.
AimsPrevious 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.
The risk of stroke in patients with atrial fibrillation (AF) can be assessed by use of the CHADS2 and the CHA2DS2-VASc score system. We hypothesised that these risk scores and their individual components could also be applied to patients paced for sick sinus syndrome (SSS) to evaluate risk of stroke and death.
Design
Prospective cohort study.
Settings
All Danish pacemaker centres and selected centres in the UK and Canada.
Patients
Risk factors were recorded prior to pacemaker implantation in 1415 patients with SSS participating in the Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber Pacing in Sick Sinus Syndrome (Danpace) trial. Development of stroke was assessed at follow-up visits and by evaluation of patient charts. Mortality was assessed from the civil registration system.
Interventions
Patients were randomised to AAIR (N=707) or DDDR pacing (N=708).
Main outcome measures
Stroke and death during follow-up.
Results
Mean follow-up was 4.3±2.5 years. In the AAIR group 6.9% patients developed stroke versus 6.1% in the DDDR group (NS). There was a significant association between CHADS2 score and the development of stroke (HR 1.41; 95% CI 1.22 to 1.64, p<0.001). CHA2DS2-VASc score was also significantly associated with stroke (HR 1.25; CI 1.12 to 1.40, p<0.001). CHADS2 score (HR 1.46; CI 1.36 to 1.56, p<0.001) and CHA2DS2-VASc score (HR 1.39; CI 1.31 to 1.46, p<0.001) were associated with mortality. Results were still significant after adjusting for AF and anticoagulation therapy.
Conclusions
CHADS2 and CHA2DS2-VASc score are associated with increased risk of stroke and death in patients paced for SSS irrespective of the presence of AF.
Purpose Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD. Methods In a nationwide Danish population-based setting, a cohort of patients with incident IBD between 1996 and 2009 were identified in national registers. Hospitalizations with IBD as primary diagnosis, initiation of biological treatment and dispensed prescriptions of corticosteroids were all used as surrogate markers for disease activity, with flares classified as the first 120 days after diagnosis of IBD, and 120 days after a new corticosteroid prescription, biological treatment or IBD hospitalization, respectively. Continued corticosteroid prescriptions or IBD hospitalizations were defined as persistent activity, and periods free of such events were defined as remissions. Poisson regression was used to examine risk of MI, stroke, and cardiovascular death using a matched population-based comparison cohort as reference Results We identified 20,795 IBD patients with a mean age of 40.3 years that were matched according to age and sex with 199,978 controls. During the study period, there were 365 patients with MI, 454 with stroke, and 778 with cardiovascular death. Patients with IBD had an overall increased risk of MI (rate ratio [RR] 1.17 [95% confidence interval 1.05–1.31]), stroke (RR 1.15 [1.04–1.27], and cardiovascular death (RR 1.35 [1.25–1.45]). During flares and persistent IBD activity the RRs of MI increased to 1.49 (1.16–1.93) and 2.05 (1.58–2.65), the RRs of stroke to 1.53 (1.22–1.92) and 1.55 (1.18–2.04) and for cardiovascular death 2.32 (2.01–2.68) and 2.50 (2.14–2.92). In remission periods, the risk of MI, stroke and cardiovascular death was similar to controls. Conclusion Inflammatory bowel disease is associated with increased risk of MI, stroke, and cardiovascular death during periods with active disease.
The aim of the study was to examine the association between self-reported alcohol intake and subsequent mortality from all causes, and to examine if the effect of alcohol intake on the risk of death was modified by sex, age, body mass index, and smoking habits. In a prospective population study of 7,234 women and 6,051 men aged 30-79 years alcohol- and tobacco consumption and body mass index were assessed in the period 1976-1978, and the population was followed until 1.1.1988 for mortality. A U-shaped curve described the relation between alcohol intake and mortality. The nadir of the risk function was observed at one to six beverages per week (relative risk set at 1.00). Abstainers had a relative risk of 1.37 (95% confidence intervals: 1.20-1.56), whereas those drinking more than 70 beverages per week had a relative risk of 2.29 (1.75-3.00). Among the drinkers, the risk was significantly higher than 1 only among those drinking more than 42 beverages per week. Neither sex, age, body mass index, nor smoking significantly modified the risk function. Our findings suggest that simple messages about the benefits of total abstinence may not be appropriate.
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