Worsening renal function (WRF) and congestion are inextricably related pathophysiologically, suggesting that WRF occurring in conjunction with persistent congestion would be associated with worse ...clinical outcome. We studied the interdependence between WRF and persistent congestion in 762 patients with acute decompensated heart failure (HF). WRF was defined as ≥0.3 mg/dl increase in serum creatinine above baseline at any time during hospitalization and persistent congestion as ≥1 sign of congestion at discharge. The primary end point was all-cause mortality with mean follow-up of 15 ± 9 months. Readmission for HF was a secondary end point. Persistent congestion was more common in patients with WRF than in patients with stable renal function (51.0% vs 26.6%, p <0.0001). Both persistent congestion and persistent WRF were significantly associated with mortality (both p <0.0001). There was a strong interaction (p = 0.003) between persistent WRF and congestion, such that the increased risk for mortality occurred predominantly with both WRF and persistent congestion. The adjusted hazard ratio for mortality in patients with persistent congestion as compared with those without was 4.16 (95% confidence interval CI 2.20 to 7.86) in patients with WRF and 1.50 (95% CI 1.16 to 1.93) in patients without WRF. In conclusion, persisted congestion is frequently associated with WRF. We have identified a substantial interaction between persistent congestion and WRF such that congestion portends increased mortality particularly when associated with WRF.
Background
Determining the pathogenesis of sudden cardiac arrest (SCA) in children is crucial for its management and prognosis. Our aim is to analyze the role of broad genetic testing in the ...prevention, diagnosis, and prognosis of SCA in Children.
Methods
ECG, 12‐lead holter, exercise testing, cardiac imaging, familial study, and genetic testing were used to study 29 families, in whom a child experienced SCA.
Results
After a thorough clinical and genetic evaluation a positive diagnosis was reached in 24/29 (83%) families. Inherited channelopathies (long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) were the most prevalent 20/29 (69%) diagnosis, followed by cardiomyopathy 3/29 (10%). Broad genetic testing was positive in 17/24 (71%) cases. Using the Mann–Whitney test, we found that genetic testing (effect size = 0.625, p = 0.003), ECG (effect size = 0.61, p = 0.009), and exercise test (effect size = 0.63, p = 0.047) had the highest yield in reaching the final diagnosis. Genetic testing was the only positive test available for five (17%) families. Among 155 family members evaluated through cascade screening, 73 (47%) had a positive clinical evaluation and 64 (41%) carried a pathologic mutation. During 6 ± 4.8 years of follow‐up, 58% of the survived children experienced an arrhythmic event. Of nine family members who had an ICD implant for primary prevention, four experienced appropriate ICD shock.
Conclusions
The major causes of SCA among children are genetic etiology, and genetic testing has a high yield. Family screening has an additional role in both the diagnosis and preventing of SCA.
ECG, 12 lead holter, exercise testing, echocardiography, familial study, and genetic testing were used to study 29 families, in whom a child experienced sudden cardiac death or sudden cardiac arrest. LQT: long QT syndrome, CPVT: catecholaminergic polymorphic ventricular tachycardia, CM cardiomyopathy.
Abstract Background Pulmonary hypertension (PH) and right ventricular (RV) dysfunction have been associated with adverse outcome in patients with chronic heart failure. However, data are lacking in ...the setting of acute decompensated heart failure (ADHF). We sought to determine prognostic significance of PH in patients with ADHF and its interaction with RV function. Methods We studied 326 patients with ADHF. Pulmonary artery systolic pressure (PASP) and RV function were determined with the use of Doppler echocardiography, with PH defined as PASP >50 mm Hg. The primary end point was all-cause mortality during 1-year follow-up. Results PH was present in 139 patients (42.6%) and RV dysfunction in 83 (25.5%). The majority of patients (70%) with RV dysfunction had PH. Compared with patients with normal RV function and without PH, the adjusted hazard ratio (HR) for mortality was 2.41 (95% confidence interval CI 1.44–4.03; P = .001) in patients with both RV dysfunction and PH. Patients with normal RV function and PH had an intermediate risk (adjusted HR 1.78, 95% CI 1.11–2.86; P = .016). Notably, patients with RV dysfunction without PH were not at increased risk for 1-year mortality (HR 1.04, 95% CI 0.43–2.41; P = .94). PH and RV function data resulted in a net reclassification improvement of 22.25% (95% CI 7.2%–37.8%; P = .004). Conclusions PH and RV function provide incremental prognostic information in ADHF. The combination of PH and RV dysfunction is particularly ominous. Thus, the estimation of PASP may be warranted in the standard assessment of ADHF.
Highlights • Hemoconcentration has been proposed as a surrogate for successful decongestion in acute heart failure. We studied the relationship between hemoconcentration and clinical measures of ...decongestion. • There was a poor correlation between the magnitude of hematocrit changes and the degree of improvement in congestion score as assessed by clinical examination. • Persistent clinical congestion at hospital discharge was present in a significant proportion of patients despite hemoconcentration (23.9%) and was associated with increased risk for mortality and heart failure rehospitalizations. • Furthermore, hemoconcentration was absent in many patients (71.0%) without clinical evidence of congestion at hospital discharge.
Background
The clinical importance of right ventricular (RV) function in acute myocardial infarction is well recognized, but the impact of concomitant pulmonary hypertension (PH) has not been ...studied.
Methods and Results
We studied 1044 patients with acute myocardial infarction. Patients were classified into 4 groups according to the presence or absence of RV dysfunction and PH, defined as pulmonary artery systolic pressure >35 mm Hg: normal right ventricle without PH (n=509), normal right ventricle and PH (n=373), RV dysfunction without PH (n=64), and RV dysfunction and PH (n=98). A landmark analysis of early (admission to 30 days) and late (31 days to 8 years) mortality and readmission for heart failure was performed. In the first 30 days, RV dysfunction without PH was associated with a high mortality risk (adjusted hazard ratio 5.56, 95% CI 2.05–15.09, P<0.0001 compared with normal RV and no PH). In contrast, after 30 days, mortality rates among patients with RV dysfunction were increased only when PH was also present. Compared with patients having neither RV dysfunction nor PH, the adjusted hazard ratio for mortality was 1.44 (95% CI 0.68–3.04, P=0.34) in RV dysfunction without PH and 2.52 (95% CI 1.64–3.87, P<0.0001) in RV dysfunction with PH. PH with or without RV dysfunction was associated with increased risk for heart failure.
Conclusion
In the absence of elevated pulmonary pressures, the risk associated with RV dysfunction after acute myocardial infarction is entirely confined to the first 30 days. Beyond 30 days, PH is the stronger risk factor for long‐term mortality and readmission for heart failure.
Objective and Background
To evaluate the diagnostic and prognostic yield of a comprehensive protocol involving clinical and broad genetic testing in consecutive sudden cardiac arrest (SCA) ...population.
Determining the pathogenesis of non‐ischemic SCA is crucial for management and SCA prevention in other family members
Methods
Families with unexplained non‐ischemic SCA event underwent rigorous clinical and genetic protocol after referral to our inherited arrhythmia clinic, during 2011–2017.
Results
One hundred and four index cases, 29 ± 16 years, and 421 family members were studied. After a thorough evaluation, diagnosis was made in 80 (77%) of families. The most prevalent 47/104 (45%) diagnosis was inherited channelopathy. The genetic test was positive, in 37 /69 (54%) of patients. Using the Mann Whitney test, we found that electrocardiography (ECG) (effect size 0.5, p < .001), 12 lead Holter (effect size 0.33, p = .001) and family screening (effect size 0.4, p = .001) had the highest yield in reaching the final diagnosis. Family screening, genetic testing, and cardiac MRI were the exclusive modalities for final diagnosis in 14%, 9%, and 2% of families, respectively. Among 421 family members evaluated through cascade screening, 127 (30%), were diagnosed and medically treated. Nine family members from 25 (40%) patients who underwent implantable cardioverter defibrillator (ICD) implantation have experienced appropriate ICD shock.
Conclusions
A rigorous, systematic protocol in a specialized inherited arrhythmia clinic has a high diagnostic and prognostic yield. ECG, 12 lead Holter and family screening significantly increased the diagnostic yield. In nine families, without genetic testing, the diagnosis would have been missed.
Rapid reperfusion is crucial to reduce mortality in patients with ST elevation myocardial infarction. Prehospital patient delay, defined as time from symptoms onset to the decision to seek medical ...attention, accounts for a large proportion of cases with delayed reperfusion. However, whether pain modulation processes are involved in this phenomenon is not known. We hypothesized that prehospital patient delay may be affected by a reduction of perceived pain perception and pain modulation pattern. Pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation and conditioned pain modulation (CPM), and recalls of pain magnitude at the onset of chest pain were obtained in 67 patients with first ST elevation myocardial infarction. The study's primary outcome was prehospital patient delay. The median patient delay was 24 (interquartile range, 0.5-72) hours. Of all psychophysical pain measures including pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation, as well as CPM, only warm sensation threshold was independently associated with lower clinical chest pain intensity (P = 0.01). Multivariable regression analysis (R = 0.449; P < 0.0001) revealed an inverse independent association between chest pain intensity (P < 0.001) and patient delay, whereas efficient CPM was positively associated with prolonged patient delay (P = 0.034). The electrocardiography-derived myocardial ischemic area was not associated with chest pain intensity or patient delay, indicating that the affected ischemic tissue is not a dominant component that determines pain response. In conclusion, beyond the perceived chest pain intensity, the activation pattern of descending inhibition pathways during coronary occlusion affects pain interpretation and behavior during acute coronary occlusion.
Dilated cardiomyopathy (DCM) caused by Lamin A/C gene (LMNA) mutation is complicated with atrioventricular conduction disturbances, malignant ventricular arrhythmias and progressive severe heart ...failure.
We hypothesized that early cardiac resynchronization therapy (CRT) implantation in LMNA mutation carriers with an established indication for pacemaker or implantable cardioverter defibrillator (ICD), may preserve ejection fraction, and delay disease progression to end stage heart failure.
We compared the primary outcomes: time to heart transplantation, death due to end stage heart failure or ventricular tachycardia (VT) ablation and secondary outcomes: change in left ventricular ejection fraction (EF) and ventricular arrhythmia burden between LMNA DCM patients in the early CRT and non-CRT groups.
Of ten LMNA DCM patients (age 51±10 years, QRS 96±14 msec, EF 55±7%) with indication for pacemaker or ICD implantation, five underwent early CRT-D implantation. After 7.2±4 years, three patients (60%) in the non-CRT group reached the primary outcome, compared to no patients in the CRT group (P=0.046). Four patients in non-CRT group (80%) experienced sustained ventricular tachycardia or received appropriate ICD shock compared to 1 patient (20%) in the CRT group (P=0.058). LMNA patients without early CRT had a higher burden of VPC/24 h in 12-lead holter (median 2352 vs 185, P=0.09). Echocardiography showed statistically lower LVEF in the non-CRT group compared to CRT group (32±15)% vs (61±4)%, 95% CI: 32.97-61.03, P=0.016.
Early CRT implantation in LMNA cardiomyopathy patients, with an indication for pacemaker or ICD, may reduce heart failure deterioration and life-threatening heart failure complications.
Aims
In the present study, we aimed to determine the relationship between therapeutic decisions during the treatment of acute heart failure (AHF) patients who develop acute kidney injury (AKI) and ...subsequent renal and clinical outcomes.
Methods and results
We studied 277 patients with AHF and AKI, defined as an increase of >0.3 mg/dL in serum creatinine. The physician response to AKI was determined through a treatment composite score that captured changes in medical management in response to AKI, including a reduction (≥50%) or discontinuation of selected medication classes angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (ACE‐Is/ARBs), beta‐blockers, and diuretics and fluids administration. ACE‐Is/ARBs, beta‐blockers, and diuretics were reduced or discontinued in 103 (55.4%), 84 (38.9%), and 166 (61.5%), respectively. Fluids were administered to 130 (46.9%) patients. Discontinuation rates of ACE‐Is/ARBs, beta‐blockers, diuretics, and fluids administration were higher in patients with hypotension (systolic blood pressure < 90 mm Hg; P = 0.001). In a logistic regression model, a composite score > 1 was associated with greater likelihood of renal function recovery (odds ratio 3.47, 95% confidence interval 2.06–5.83; P < 0.0001) but with a smaller reduction in congestion index (P = 0.021). Unadjusted 6 months mortality was higher in patients with a composite treatment score > 1 (hazard ratio 1.71, 95% confidence interval 1.12–2.61; P = 0.01). After adjustments, the treatment composite score was no longer associated with mortality.
Conclusions
Discontinuation or dose reduction of diuretics or neurohormonal blockers may improve renal outcome at the price of less efficient decongestion. Our results emphasize the need for randomized clinical trials that address the treatment of AHF patients with AKI.
Aims
The acute (type 1) cardio‐renal syndrome (CRS) refers to an acute worsening of heart function leading to worsening renal function (WRF), and frequently complicates acute decompensated heart ...failure (ADHF) and acute myocardial infarction (AMI). The aim of this study was to investigate whether hyponatraemia, a surrogate marker of congestion and haemodilution and of neurohormonal activation, could identify patients at risk for WRF.
Methods and results
We studied the association between hyponatraemia (sodium <136 mmol/L) and WRF (defined as an increase of >0.3 mg/dL in creatinine above baseline) in two separate cohorts: patients with ADHF (n = 525) and patients with AMI (n = 2576). Hyponatraemia on admission was present in 156 patients (19.7%) with ADHF and 461 patients (17.7%) with AMI. Hyponatraemia was more frequent in patients who subsequently developed WRF as compared with patients who did not, in both the ADHF (34.6% vs. 22.2%, P = 0.0003) and AMI (29.7% vs. 21.8%, P<0.01) cohorts. In a multivariable logistic regression model, the multivariable adjusted odds ratio for WRF was 1.90 95% confidence interval (CI) 1.25–2.88; P = 0.003 and 1.56 (95% CI 1.13–2.16; P = 0.002) in the ADHF and AMI cohorts, respectively. The mortality risk associated with hyponatraemia was attenuated in the absence of WRF.
Conclusion
Hyponatraemia predicts the development of WRF in two clinical scenarios that frequently lead to the type I CRS. These data are consistent with the concept that congestion and neurohormonal activation play a pivotal role in the pathophysiology of acute cardio‐renal failure.
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