Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 2014.

Aims: We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence-based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and results: Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. Conclusion: In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and reduction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.

Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995-2014.

AIMS: Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. METHODS AND RESULTS: All STEMI cases (n = 105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend <0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P < 0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906-0.923) per 2-year period which no longer was significant, 0.997 (0.984-1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. CONCLUSION: Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.

Adrenergic and cardiac dysfunction in primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death, but the underlying mechanisms are incompletely understood. The aim of this study was to investigate whether adrenergic dysfunction may be a contributing factor. PATIENTS AND METHODS: Forty-nine patients with mild PHPT (serum calcium 2·7 ± 0·1 mM) and 48 control subjects, matched for age and sex, were examined; patients within 1 month before parathyroidectomy (PTX) and 6 months postoperatively; control subjects at inclusion. Heart rate variability (HRV) was analysed in 24-h electrocardiograms, and plasma concentrations of epinephrine and norepinephrine were measured at rest and immediately after standardized physical tests. RESULTS: At baseline, the patients showed, compared to the controls, reduced stress-related increase of circulating epinephrine (P < 0·05) and norepinephrine (P < 0·05). No significant change was observed 6 months after PTX. At baseline, there were no significant differences between patients and controls in HRV or heart rate, but 6 months after curative PTX, the patients showed significantly reduced HRV in both frequency and time domain, and their maximum and average heart rate had decreased (P = 0·011 and P = 0·018, respectively). The patients with the highest preoperative levels of circulating parathyroid hormone showed the greatest changes in heart rate and HRV postoperatively. CONCLUSIONS: This study demonstrates a previously unknown impairment of catecholamine response to physical stress in PHPT along with changes of HRV, also indicating adrenergic dysfunction. These factors should be considered in the ongoing controversy regarding the management of patients with mild 'asymptomatic' PHPT.

Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.

OBJECTIVE: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19. METHODS: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019. RESULTS: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic. CONCLUSION: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.

Natriuretic peptides as indicators of cardiac remodeling in hypertensive patients.

AIMS: This study was performed to evaluate the relationship between three different natriuretic peptides and left ventricular mass, function and diameter, and kidney function in patients with hypertension. METHODS: One hundred and thirty-nine patients with moderate hypertension were consecutively included. N-terminal brain natriuretic peptide (Nt-BNP), brain natriuretic peptide (BNP) and N-terminal pro-atrial natriuretic peptide (Nt-ANP) were analyzed. Cardiac remodeling was assessed by echocardiography (UCG) and glomerular filtration was estimated by cystatin C. RESULTS: Patients were stratified into four groups with regard to the extent of cardiac remodeling: (1) no remodeling; (2) one of left ventricular hypertrophy, left ventricular dysfunction or left ventricular dilatation; (3) two of above and (4) all three parameters. All peptides differed significantly between the groups (all p<0.001), with a continuous stepwise increase from groups 1 through 4. Receiver operating characteristic analysis showed equal diagnostic performances for the detection of any cardiac abnormalities for Nt-BNP [area under curve, AUC=0.63 (0.52-0.75), p=0.026] and BNP [AUC=0.64 (0.53-0.76), p=0.019], both, however superior to Nt-ANP [AUC=0.59 (0.47-0.70), p=0.139]. In multivariable linear regression analysis, all three indicators of cardiac remodeling were independently correlated with ln Nt-BNP and ln BNP, whereas only left ventricular diameter was independently correlated with ln Nt-ANP. CONCLUSIONS: Natriuretic peptide levels increased with increasing number of markers of cardiac remodeling. Nt-BNP and BNP are useful to discriminate between patients with regard to cardiac remodeling and might be considered a screening tool in order select patients eligible for further examination with UCG examination.

Visually estimated left ventricular ejection fraction by echocardiography is closely correlated with formal quantitative methods.

BACKGROUND: Simpson ejection fraction, wall motion score index, atrioventricular (AV) plane displacement and fractional shortening are all established formal echocardiographic methods for the assessment of left ventricular systolic function. Visually estimated (eyeballing) ejection fraction may be considered somewhat more subjective, although shown to correlate well with radionuclide ventriculography. We aimed to explore if echocardiographic eyeballing ejection fraction is comparable to formal methods for the evaluation of left ventricular systolic function. METHODS: We assessed 89 consecutive patients after myocardial infarction or before coronary angiography. Eyeballing ejection fraction and wall motion score index were evaluated in the long-axis, short-axis and apical four- and two-chamber views. Simpson ejection fraction and AV plane displacement were assessed in the apical views. Fractional shortening was measured in the parasternal long-axis view. The respective systolic function measurements were in each patient made at different time points by a single investigator, masked to prior results. RESULTS: All formal methods correlated significantly with eyeballing ejection fraction (p<0.001): AV plane displacement, R=0.647; FS, R=0.684; four-chamber Simpson ejection fraction, R=0.857; biplane Simpson ejection fraction, R=0.898; and wall motion score index, R=0.919. CONCLUSION: Eyeballing ejection fraction correlated closely with all formal methods and the correlation coefficient improved with the reliability of the formal method. This finding is in concordance with prior studies, indicating that eyeballing ejection fraction may be the most accurate echocardiographic method for the assessment of left ventricular systolic function. Since it is readily and quickly performed, eyeballing ejection fraction could be used for routine echocardiography instead of formal methods.

The prevalence of impaired left ventricular diastolic filling is related to the extent of coronary atherosclerosis in patients with stable coronary artery disease.

AIMS: The relation between abnormal left ventricular (LV) diastolic filling and the extent of coronary atherosclerosis per se has not been described. We aimed to investigate the prevalence of impaired LV diastolic filling in patients with stable coronary artery disease (CAD) and its relationship to the number and location of coronary lesions visualized at coronary angiography. METHODS AND RESULTS: In 170 consecutive patients with stable CAD and an abnormal coronary angiogram we assessed LV diastolic filling by Doppler evaluation of the transmitral early to atrial peak flow velocity (E/A) and the systolic to diastolic ratio of the pulmonary venous peak inflow to the left atrium (S/D). Abnormal diastolic filling was defined as E/A < or =0.75, or E/A >1.0 combined with S/D < or =1.0, and was present in 41% of the patients. In patients with one-, two- and three-vessel disease the prevalence of impaired diastolic filling was 27, 30 and 49%, respectively (P = 0.026). In multiple logistic regression analysis diastolic filling was independently correlated with the number of stenotic coronary vessel areas. CONCLUSION: In patients with stable angiographically verified CAD, the prevalence of impaired diastolic filling was 41%. The prevalence increased with an increasing number of stenotic coronary artery areas independent of other variables tested, including prior myocardial infarction, LV systolic function and mitral regurgitation.

Prognostication and risk stratification by assessment of left atrioventricular plane displacement in patients with myocardial infarction.

BACKGROUND: Mean left atrioventricular plane displacement is strongly related to prognosis in patients with heart failure. We aimed to examine its value for prognostication and risk stratification in patients hospitalised for acute myocardial infarction. METHODS AND RESULTS: Left atrioventricular plane displacement was assessed by echocardiography in 271 consecutive patients with acute myocardial infarction. Mean prospective follow-up was 628 days. Atrioventricular plane displacement was readily assessed in all patients and was significantly lower in patients who died (n=41, 15.1%) compared to the survivors: 8.2(5.6) v. 10.0(5.5) mm, P<0.0001. Overall mortality was 31.3% in the lowest quartile with regard to atrioventricular plane displacement (<8.00 mm) and 10.1% in the combined upper three quartiles. Thus, the hazard ratio for an atrioventricular plane displacement <8.0 mm compared to 8 mm or more was 3.1, P=0.0001. The combined mortality/heart failure hospitalisation incidence was 43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio 3.0, P<0.0001. In multivariate analysis, including age and history of atrial fibrillation, left atrioventricular plane displacement was an independent prognostic marker. CONCLUSION: In post-myocardial infarction patients, echocardiographic assessment of atrioventricular plane displacement showed a strong, independent prognostic value. Determination of left atrioventricular plane displacement can be readily performed in virtually all patients, and may in clinical practice facilitate identification of high-risk patients.

Left atrioventricular plane displacement predicts cardiac mortality in patients with chronic atrial fibrillation.

AIM: The aim of the present study was to investigate if left atrioventricular plane displacement (AVPD) has a prognostic value in patients with atrial fibrillation. METHODS AND RESULTS: Left AVPD was assessed by two-dimensionally guided M-mode echocardiography in the four- and two-chamber views in 160 consecutive patients with chronic atrial fibrillation, who were followed up with regard to mortality for an average of 45 months. All-cause mortality during follow-up was 49% (n=78). AVPD was lower in patients who died compared to those who survived: 6.6+/-1.7 versus 7.5+/-1.7 mm, P=0.0005. In 49 patients (31%), death was due to chronic heart failure or acute myocardial infarction. Among those who died of cardiac events, AVPD was 6.3+/-1.6 mm, versus 7.1+/-1.8 mm among those who died of other causes, P=0.0001. In multiple logistic regression analysis, AVPD (P=0.005), age (P=0.0005), and a history of chronic heart failure (P=0.004) correlated independently with mortality. CONCLUSION: Left AVPD was clearly decreased in patients with atrial fibrillation. The decrease was most pronounced in patients who died of cardiac events, whereas it did not differ significantly between those who died of non-cardiac causes and those who survived. The discriminative value of left AVPD was limited.

Safety and efficacy of valsartan versus enalapril in heart failure patients.

Although a cornerstone in the treatment of heart failure, angiotensin-converting enzyme inhibitors are under-used, partly due to side effects. If proven at least similarly efficacious to angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers may replace them due to their superior tolerability. We aimed to compare the efficacy and safety of valsartan and enalapril in heart failure patients stabilised on an angiotensin-converting enzyme inhibitor. We randomised 141 patients (mean 68 years, 74% males) with stable mild/moderate heart failure and left ventricular ejection fraction 0.45 or less, to valsartan 160 mg q.d. (n=70) or enalapril 10 mg b.i.d. (n=71) for 12 weeks. Changes in 6-min-walk test (primary efficacy variable), patients' wellbeing and left ventricular size and function did not differ significantly between the treatment groups. Valsartan was significantly non-inferior to enalapril in walk test distance change: least-square means treatment difference +1.12 m (95% confidence interval -21.9 to 24.1), non-inferiority P<0.001. Left ventricular size (P<0.001) and function (P=0.048) improved significantly only in the valsartan group. Fewer patients experienced adverse events in the valsartan group (50%) than in the enalapril group (63%), although statistically non-significant. Valsartan is similarly efficacious and safe to enalapril in patients with stable, mild/moderate heart failure, previously stabilised on an angiotensin-converting enzyme inhibitor and directly switched to study medication.

Effect of successful parathyroidectomy on 24-hour ambulatory blood pressure in patients with primary hyperparathyroidism.

OBJECTIVE: The pathogenesis of hypertension in patients with primary hyperparathyroidism (PHPT) is unclear, and the prevailing opinion is that parathyroidectomy does not affect the blood pressure (BP). Most previous studies have been based on BP measurements at rest in a clinical setting. The aim of this study was to get additional information by 24-hour ambulatory measurements. DESIGN AND PATIENTS: Forty-nine consecutive patients with PHPT (age 63+/-12 years, 44 women) were examined before and 6 months after curative parathyroid surgery. MEASUREMENTS: Serum concentrations of calcium and PTH, and 24-hour ambulatory mean, minimum, and maximum systolic (S) and diastolic BP, and mean arterial BP. RESULTS: On average, the patients showed no BP change after parathyroidectomy. However, those with a history of hypertension (n=20) showed generally increased BP values after parathyroidectomy, with significantly increased minimum and average SBP (P=0.02 and P=0.04, respectively), whereas patients without a history of hypertension (n=29) showed unchanged or slightly reduced BP values after parathyroidectomy, with significantly decreased maximum SBP (P=0.04). Serum concentrations of PTH and calcium were not significantly related to any of the BP variables measured. CONCLUSIONS: The novel finding that patients with both PHPT and hypertension may show increased BP after parathyroidectomy warrants intensified BP control postoperatively in these patients, and motivates early treatment of PHPT in order to prevent the development of complicating hypertension.

Primary hyperparathyroidism and heart disease--a review.

Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in 85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as constipation, fatigue and weakness are well-known complications. However, in Western Europe and North America, patients with pHPT are nowadays usually discovered during an early, asymptomatic phase of the disease. It has been reported that patients suffering from symptomatic pHPT have increased mortality, mainly due to an overrepresentation of cardiovascular death. pHPT is reported to be associated with hypertension, disturbances in the renin-angiotensin-aldosterone system, and structural and functional alterations in the vascular wall. Recently, studies have indicated an association between pHPT and heart disease, and studies in vitro have produced a number of theoretical approaches. An increased prevalence of cardiac structural abnormalities such as left ventricular hypertrophy (LVH) and valvular and myocardial calcification has been observed. Associations have been found between PTH and LVH, and between LVH and serum calcium. LV systolic function does not seem to be affected in patients with pHPT, whereas any influence on LV diastolic performance needs further evaluation. The aim of this review is to clarify the connection between pHPT and cardiac disease.