Validation of the 30-Year Framingham Risk Score in a German Population-Based Cohort

The Framingham Risk Score to predict 30-year risk (FRS30y) of cardiovascular disease (CVD) constitutes an important tool for long-term risk prediction. However, due to its complex statistical properties and the paucity of large population-based cohorts with appropriate data, validation of the FRS30y is lacking. A population-based cohort from Southern Germany (N = 3110, 1516 (48.7%) women) was followed up for a median time of 29.5 [18.7, 31.2] years. Discrimination and calibration were assessed for the original, recalibrated and refitted FRS30y version. During follow up, 620 incident CVD events (214 in women) occurred. The FRS30y showed adequate discrimination (original and recalibrated version: Area under the curve (AUC): 78.4 for women and 74.9 for men) but overestimated actual CVD risk (original version: discordance 45.4% for women and 37.3% for men, recalibrated version: 37.6% and 28.6%, respectively). Refitting showed substantial improvement in neither discrimination nor calibration. The performance of FRS30y is adequate for long-term CVD risk prediction and could serve as an important tool in risk communication, especially for younger audiences

Heart Rate Response During Treadmill Exercise Test in Children and Adolescents With Congenital Heart Disease

Background: Impaired exercise capacity is a common feature of congenital heart disease (CHD). In adults with CHD, it has been shown that impaired heart rate response during exercise may contribute to exercise limitation. Systematic data in children and adolescents on this topic is limited. We therefore purposed to assess heart rate response during treadmill exercise testing in children and adolescents with CHD compared to healthy controls.Methods: One hundred and sixty three children and adolescents (103 with CHD, median age 15 years and 60 age-matched controls) performed cardiopulmonary exercise testing and were included in this study. Beyond peak oxygen consumption, increase in heart rate from resting level to peak exercise (heart rate reserve) and decrease of heart rate after peak exercise (heart rate recovery) were measured. Chronotropic index was defined as percentage of age predicted maximal heart rate reserve. According to data from adults on bicycle exercise, chronotropic incompetence was assumed for chronotropic index below 0.8.Results: While resting heart rate was similar between both groups, peak heart rate, heart rate reserve as well as chronotropic index were lower in the CHD group than in controls. Chronotropic index was lowest in patients with single ventricle hemodynamics and correlated with peak oxygen consumption. Heart rate recovery was impaired in the CHD group 1 and 2 min after peak exercise compared to controls and correlated with peak oxygen consumption. Chronotropic index below 0.8 was a relatively frequent finding even in the control group suggesting that the threshold of 0.8 appears inadequate for the identification of chronotropic incompetence using treadmill exercise testing in children. After normalizing to the 2.5th chronotropic index percentile of the control group we obtained a chronotropic incompetence threshold of 0.69.Conclusion: As an adjunct to measurement of peak oxygen consumption, heart rate response to exercise appears to be a physiologically important diagnostic parameter in children and adolescents with CHD. However, interpretation of heart rate response needs to consider specific age characteristics and the mode of exercise test. Our data may help future studies on chronotropic incompetence using treadmill ergometer protocols in children and adolescents

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Autologe Stammzelltherapie nach akutem Myokardinfarkt

Es existieren widersprüchliche Ergebnisse zur Verbesserung der Myokardfunktion durch Applikation autologer Knochenmarkstammzellen (BMC) nach akutem Myokardinfarkt (AMI). Diese Studie wurde randomisiert, doppelblind und Placebo kontrolliert durchgeführt. Die Studienpopulation umfasste Patienten mit großem AMI, mit erfolgreicher Reperfusion mittels perkutaner Koronarintervention (PCI) später als 6 Stunden nach Symptombeginn. Eine Stratifizierung wurde nach Alter, Infarktlokalisation und Einschränkung der linksventrikulären Funktion vorgenommen. Die Studientherapie wurde median 6,1 Tage nach Symptombeginn appliziert. Im Schnitt wurden im Therapiearm 3,81*108 BMCs mit Stop-Flow Technik intrakoronar injiziert. MRT Untersuchungen der Patienten fanden zu den Zeitpunkten initial vor Applikation der Studientherapie sowie nach 1, 3 und 6 Monaten statt. Primärer Endpunkt war die Differenz der LVEF zwischen den Zeitpunkten initial und 6 Monaten gemessen mittels Kardio-MRT. Sekundäre Endpunkte waren die Infarktgröße im Verlauf sowie die Veränderung der linksventrikulären enddiastolischen und endsystolischen Volumenindices (LVEDVI, LVESVI). Bezogen auf den Startzeitpunkt lag die Veränderung der LVEF nach sechs Monaten in der Therapiegruppe bei 1,8 ± 5,3 % und in der Placebogruppe bei 5,7 ± 8,4 % (p = 0,88). Auch zu keinem früheren Zeitpunkt war eine Überlegenheit der BMC-Gruppe zu finden. Die Auswertung der sekundären Endpunkte Infarktgröße, LVEDVI und LVESVI zeigte keinen relevanten Unterschied zwischen den beiden Studiengruppen. In dieser randomisierten, Placebo kontrollierten Doppelblindstudie konnte kein Hinweis für einen positiven Effekt einer autologen BMC-Transplantation im Vergleich zu einer Placebobehandlung bei AMI mit erfolgreicher PCI später als 6 Stunden nach Symptombeginn nachgewiesen werden

Surprising Echo Findings as First Diagnosis of Congenital Heart Disease in Adulthood

Congenital heart defects (AHF) are sometimes not diagnosed until adulthood; either because they only become clinically apparent later in life or were overlooked until then. During routine transthoracic echocardiography (TTE) examination in the cardiology practice or clinic, cardiac abnormalities can be suspected and patients should be referred for further diagnosis to a center with AHF expertise. This requires knowledge of the echocardiographic presentation of AHF. Since the focus of adult cardiology is predominantly on acquired cardiac disease such as dilated or ischemic cardiomyopathy, valve dysfunction, or ventricular dysfunction, dealing with AHF often plays a minor role. Therefore, the expectation regarding congenital cardiac anomalies is not particularly high and the eye for possible - in clinical routine more frequent or rare - cardiac defects often not sharpened. This article presents the most common AHF and their echocardiographic findings to help increase the likelihood of detecting an AHF by TTE in clinical practice

Left Ventricular Strain Analysis During Submaximal Semisupine Bicycle Exercise Stress Echocardiography in Childhood Cancer Survivors

Background Childhood cancer survivors (CCSs) show relevant cardiac morbidity and mortality throughout life. Early detection is key for optimal support of patients at risk. The aim of this study was to evaluate 2‐dimensional speckle‐tracking echocardiography strain analysis during semisupine exercise stress in CCSs for detection of subclinical left ventricular dysfunction after cancer treatment. Methods and Results Seventy‐seven CCSs ≥1‐year postchemotherapy were prospectively examined at rest, low, and submaximal stress level and compared with a cohort of healthy adolescents and young adults (n=50). Global longitudinal strain (GLS), short axis circumferential strain, and corresponding strain rates were analyzed using vendor‐independent software. CCSs at median 7.8 years postchemotherapy showed comparable left ventricular GLS, circumferential strain, and strain rate values at all stress stages to healthy controls. Yet, prevalence of abnormal GLS (defined as <2 SD of controls reference) in CCSs was 1.3% at rest, 2.7% at low, and 8.6% at submaximal stress. In CCSs, relative change of circumferential strain from rest to submaximal stress was lower than in healthy controls, median 16.9 (interquartile range [IQR], 3.4; 28.8) % versus 23.3 (IQR, 11.3; 33.3) %, P=0.03, most apparent in the subgroups of CCSs after high‐dose anthracycline treatment and cancer diagnosis before the age of 5 years. Conclusions In this prospective 2‐dimensional speckle tracking echocardiography strain study, prevalence of abnormal left ventricular GLS increased with stress level reflecting impaired cardiac adaptation to exercise stress in some CCSs. However, relatively early after last chemotherapy, this did not result in significant differences of mean GLS‐, circumferential strain‐, and strain rate values between CCSs and controls at any stress level

D-Dimer Predicts Disease Severity but Not Long-Term Prognosis in Acute Pulmonary Embolism

D-dimer might be correlated with prognosis in pulmonary embolism (PE). The predictive value of plasma D-dimer for disease severity and survival was investigated in the lowest and highest D-dimer quartile among 200 patients with PE. Patients with high D-dimers were significantly more often hypotensive (P = .001), tachycardic (P = .016), or hypoxemic (P = .001). Pulmonary arterial obstruction index (PAOI) values were significantly higher in the high D-dimer quartile (P = 1 (P = 1 (P = 1 (P = .021), elevated PAOI (P < .001) or TNI levels (P < .001), hypotension (P < .001), tachycardia (P = .003), and hypoxemia (P < .001), but not with long-term all-cause mortality. D-dimer predicts disease severity but not long-term prognosis in acute PE, possibly due to a more aggressive treatment strategy in severely affected patients

D-Dimer predicts disease severity but not long-term prognosis in acute pulmonary embolism

D-dimer might be correlated with prognosis in pulmonary embolism (PE). The predictive value of plasma D-dimer for disease severity and survival was investigated in the lowest and highest D-dimer quartile among 200 patients with PE. Patients with high D-dimers were significantly more often hypotensive (P = .001), tachycardic (P = .016), or hypoxemic (P = .001). Pulmonary arterial obstruction index (PAOI) values were significantly higher in the high D-dimer quartile (P = 1 (P = 1 (P = 1 (P = .021), elevated PAOI (P < .001) or TNI levels (P < .001), hypotension (P < .001), tachycardia (P = .003), and hypoxemia (P < .001), but not with long-term all-cause mortality. D-dimer predicts disease severity but not long-term prognosis in acute PE, possibly due to a more aggressive treatment strategy in severely affected patients