Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Left ventricular thrombus formation in myocardial infarction is associated with altered left ventricular blood flow energetics.

Aims: The main aim of this study was to characterize changes in the left ventricular (LV) blood flow kinetic energy (KE) using four-dimensional (4D) flow cardiovascular magnetic resonance imaging (CMR) in patients with myocardial infarction (MI) with/without LV thrombus (LVT). Methods and results: This is a prospective cohort study of 108 subjects [controls = 40, MI patients without LVT (LVT- = 36), and MI patients with LVT (LVT+ = 32)]. All underwent CMR including whole-heart 4D flow. LV blood flow KE wall calculated using the formula: KE=12 ρblood . Vvoxel . v2, where ρ = density, V = volume, v = velocity, and was indexed to LV end-diastolic volume. Patient with MI had significantly lower LV KE components than controls (P < 0.05). LVT+ and LVT- patients had comparable infarct size and apical regional wall motion score (P > 0.05). The relative drop in A-wave KE from mid-ventricle to apex and the proportion of in-plane KE were higher in patients with LVT+ compared with LVT- (87 ± 9% vs. 78 ± 14%, P = 0.02; 40 ± 5% vs. 36 ± 7%, P = 0.04, respectively). The time difference of peak E-wave KE demonstrated a significant rise between the two groups (LVT-: 38 ± 38 ms vs. LVT+: 62 ± 56 ms, P = 0.04). In logistic-regression, the relative drop in A-wave KE (beta = 11.5, P = 0.002) demonstrated the strongest association with LVT. Conclusion: Patients with MI have reduced global LV flow KE. Additionally, MI patients with LVT have significantly reduced and delayed wash-in of the LV. The relative drop of distal intra-ventricular A-wave KE, which represents the distal late-diastolic wash-in of the LV, is most strongly associated with the presence of LVT.

Myocardial strain and symptom severity in severe aortic stenosis: insights from cardiovascular magnetic resonance.

BACKGROUND: Symptomatic severe aortic stenosis (AS) is a class I indication for replacement in patients when left ventricular ejection fraction (LVEF) is preserved. However, symptom reporting is often equivocal and decision making can be challenging. We aimed to quantify myocardial deformation using cardiovascular magnetic resonance (CMR) in patients classified by symptom severity. METHODS: Forty-two patients with severe AS referred to heart valve clinic were studied using tagged CMR imaging. All had preserved LVEF. Patients were grouped by symptoms as either "none/mild" (n=21, NYHA class I, II) or "significant" (n=21, NYHA class III, IV, angina, syncope) but were comparable for age (72.8±5.4 vs. 71.0±6.8 years old, P=0.345), surgical risk (EuroSCORE II: 1.90±1.7 vs. 1.31±0.4, P=0.302) and haemodynamics (peak aortic gradient: 55.1±20.8 vs. 50.4±15.6, P=0.450). Thirteen controls matched in age and LVEF were also studied. LV circumferential strain was calculated using inTag© software and longitudinal strain using feature tracking analysis. RESULTS: Compared to healthy controls, patients with severe AS had significantly worse longitudinal and circumferential strain, regardless of symptom status. Patients with "significant" symptoms had significantly worse peak longitudinal systolic strain rates (-83.352±24.802%/s vs. -106.301±43.276%/s, P=0.048) than those with "no/mild" symptoms, with comparable peak longitudinal strain (PLS), peak circumferential strain and systolic and diastolic strain rates. CONCLUSIONS: Patients with severe AS who have no or only mild symptoms exhibit comparable reduction in circumferential and longitudinal fibre function to those with significant symptoms, in whom AVR is clearly indicated. Given these findings of equivalent subclinical dysfunction, reportedly borderline symptoms should be handled cautiously to avoid potentially adverse delays in intervention.

Quinine for muscle cramps.

BACKGROUND: Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. This review was first published in 2010 and searches were updated in 2014. OBJECTIVES: To assess the efficacy and safety of quinine-based agents in treating muscle cramps. SEARCH METHODS: On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. We searched reference lists of articles up to 2014. We also searched for ongoing trials in November 2014. SELECTION CRITERIA: Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. For comparisons including more than one trial, we assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). MAIN RESULTS: We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014.The risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately.Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events. AUTHORS' CONCLUSIONS: There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.There is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.

Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla.

BACKGROUND: Intramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T. METHODS: Forty-nine patients (42 males; mean age 58 years, range 35-76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent). RESULTS: Of 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p = ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ = 0.90 and κ = 0.88 respectively); both had higher reliability than T2 star (κ = 0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p < 0.01). CONCLUSIONS: SW MRI is an accurate and reproducible way to detect IMH at 3T. The technique offers considerably shorter breath hold times than T2-weighted and T2 star imaging, and higher image quality scores.

Primary cardiac tumors: 32 years of experience from a Spanish tertiary surgical center.

INTRODUCTION: Primary cardiac tumors are rare entities with an autopsy frequency ranging between 0.001% and 0.3%. Our objective was to review 32 years of experience from a Spanish tertiary surgical center. METHOD: We collected data on 73 patients with a histopathological diagnosis of a primary cardiac tumor in a retrospective analysis from 1979 to 2012. Tissue samples were obtained either at surgery or from necropsy and subsequently divided into benign and malignant groups. RESULTS: Benign neoplasms accounted for 84.9% of cases. The average age at diagnosis was 61 years, and tumors were twice as frequent among women. It was an incidental finding in one quarter of patients. In symptomatic patients, the typical presentation was of cardioembolic stroke or of congestive symptoms. Myxoma (93.5%) was the most common diagnosis, typically affecting the left atrium (74.2%). Surgical resection was curative for 95% of these patients. Malignant tumors represented 15.1% of cases with an average age at diagnosis of 50 years. Over 90% of these patients were symptomatic at presentation with the cardinal symptom being heart failure. Undifferentiated sarcoma was the most frequent malignant tumor (36.4%). Less than 20% of patients were alive 1 year after diagnosis despite the treatment. CONCLUSIONS: In our study, primary cardiac tumors were insidious. The most common was left atrial myxoma in which surgical resection was considered curative. Undifferentiated sarcoma was the most frequent malignant tumor. Malignant neoplasms carried a worse prognosis with unsuccessful total excision and the presence of metastatic disease being markers of an adverse outcome.

Quinine for muscle cramps.

BACKGROUND: Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. OBJECTIVES: To assess the efficacy and safety of quinine in treating muscle cramps. SEARCH STRATEGY: We searched The Cochrane Neuromuscular Disease Group Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), MEDLINE, EMBASE and reference lists of articles up to July 2010. SELECTION CRITERIA: Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives. DATA COLLECTION AND ANALYSIS: Three authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. MAIN RESULTS: We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n =1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg).Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference +3%, 95% confidence intervals 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (risk difference 0%, 95% confidence intervals -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events. AUTHORS' CONCLUSIONS: There is moderate quality evidence that quinine significantly reduces cramp frequency, intensity and cramp days in dosages between 200 and 500 mg/day. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials. Further research is required on the optimal dose and duration of use, and also on alternative treatments.