The Degree of the Predischarge Pulmonary Congestion in Patients Hospitalized for Worsening Heart Failure Predicts Readmission and Mortality.

BACKGROUND: Prediction of readmission and death after hospitalization for heart failure (HF) is an unmet need. AIM: We evaluated the ability of clinical parameters, NT-proBNP level and noninvasive lung impedance (LI), to predict time to readmission (TTR) and time to death (TTD). METHODS AND RESULTS: The present study is a post hoc analysis of the IMPEDANCE-HF extended trial comprising 290 patients with LVEF ≤45% and New York Heart Association functional class II-IV, randomized 1:1 to LI-guided or conventional therapy. Of all patients, 206 were admitted 766 times for HF during a follow-up of 57 ± 39 months. The normal LI (NLI), representing the "dry" lung status, was calculated for each patient at study entry. The current degree of pulmonary congestion (PC) compared with its dry status was represented by ΔLIR = ([measured LI/NLI] - 1) × 100%. Twenty-six parameters recorded during HF admission were used to predict TTR and TTD. To determine the parameter which mainly impacted TTR and TTD, variables were standardized, and effect size (ES) was calculated. Multivariate analysis by the Andersen-Gill model demonstrated that ΔLIRadmission (ES = 0.72), ΔLIRdischarge (ES = -3.14), group assignment (ES = 0.2), maximal troponin during HF admission (ES = 0.19), LVEF related to admission (ES = -0.22) and arterial hypertension (ES = 0.12) are independent predictors of TTR (p < 0.01, χ2 = 1,206). Analysis of ES showed that residual PC assessed by ∆LIRdischarge was the most prominent predictor of TTR. One percent improvement in predischarge PC, assessed by ∆LIRdischarge, was associated with a likelihood of TTR increase by 14% (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.13-1.15, p < 0.01) and TTD increase by 8% (HR 1.08, 95% CI 1.07-1.09, p < 0.01). CONCLUSION: The degree of predischarge PC assessed by ∆LIR is the most dominant predictor of TTR and TTD.

[DIRECT ADMISSION OF STEMI PATIENTS TO THE CARDIAC CARE UNIT VERSUS ADMISSION VIA THE EMERGENCY DEPARTMENT FOR PRIMARY CORONARY INTERVENTION IMPROVES SHORT AND LONG-TERM SURVIVAL].

INTRODUCTION: Shortening door-to-balloon time intervals in ST-elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI) is necessary in order to limit myocardial damage. Direct admission to the cardiac care unit (CCU) facilitates this goal. We compared characteristics and short- and long-term mortality of PPCI-treated STEMI patients admitted directly to the CCU with those admitted via the emergency department (ED). METHODS: To compare 303 patients admitted directly to the CCU (42%) with 427 admitted via the ED (58%) included in the current registry comprising 730 consecutive PPCI-treated STEMI patients. RESULTS: Groups were similar regarding demographics, medical history and risk factors. Pain-to-CCU time was 151±164 minutes (median-94) for patients admitted directly and 242±226 minutes (160) for those admitted via the ED, while door-to-balloon intervals were 69±42 minutes (61) and 133±102 minutes (111), respectively. LVEF evaluated during admission (48.3±13% [47.5%] vs. 47.7±13.7% [47.5%]) and mean CK level (893±1157 [527] vs. 891±1255 [507], p=0.45) were similar between groups. Mortality was 4.2% vs. 10.3% at 30-days (p<0.002), 7.6% and 14.3% at one-year (p<0.01), reaching 12.2% and 21.9% at 3.9±2.3 years (median-3.5, p<0.004) among directly-admitted patients vs. those admitted via the ED, respectively. Long-term mortality was 4.1%, 9.4%, 21.4%, and 16% for pain-to-balloon quartiles of <140 min, 141-207 min, 208-330 min, and >330 mins, respectively (p=0.026). CONCLUSIONS: Direct admission of STEMI patients to the CCU for PPCI facilitated the attainment of guidelines-dictated door-to-balloon time intervals and yielded improved short- and long-term mortality. Longer pain-to-balloon time was associated with higher long-term mortality.

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Primary Percutaneous Coronary Intervention Versus In-hospital thrombolysis as Reperfusion Therapy in Early-Arriving Low-risk STEMI Patients.

BACKGROUND: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. OBJECTIVES: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients. METHODS: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only. RESULTS: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12). CONCLUSIONS: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.

Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients: A Randomized Controlled Trial (IMPEDANCE-HF Trial).

BACKGROUND: Previous investigations have suggested that lung impedance (LI)-guided treatment reduces hospitalizations for acute heart failure (AHF). A single-blind 2-center trial was performed to evaluate this hypothesis (ClinicalTrials.gov-NCT01315223). METHODS: The study population included 256 patients from 2 medical centers with chronic heart failure and left ventricular ejection fraction ≤35% in New York Heart Association class II-IV, who were admitted for AHF within 12 months before recruitment. Patients were randomized to a control group treated by clinical assessment and a monitored group whose therapy was also assisted by LI, and followed for at least 12 months. Noninvasive LI measurements were performed with a new high-sensitivity device. Patients, blinded to their assignment group, were scheduled for monthly visits in the outpatient clinics. The primary efficacy endpoint was AHF hospitalizations; the secondary endpoints were all-cause hospitalizations and mortality. RESULTS: There were 67 vs 158 AHF hospitalizations during the first year (P < .001) and 211 vs 386 AHF hospitalizations (P < .001) during the entire follow-up among the monitored patients (48 ± 32 months) and control patients (39 ± 26 months, P = .01), respectively. During the follow-up, there were 42 and 59 deaths (hazard ratio 0.52, 95% confidence interval 0.35-0.78, P = .002) with 13 and 31 of them resulting from heart failure (hazard ratio 0.30, 95% confidence interval 0.15-0.58 P < .001) in the monitored and control groups, respectively. The incidence of noncardiovascular death was similar. CONCLUSION: Our results seem to validate the concept that LI-guided preemptive treatment of chronic heart failure patients reduces hospitalizations for AHF as well as the incidence of heart failure, cardiovascular, and all-cause mortality.

Novel Method for Real Time Co-Registration of IVUS and Coronary Angiography.

OBJECTIVES: We present our experience with a novel method for real time co-registration of intravascular ultrasound (IVUS) and coronary angiography. BACKGROUND: A major limitation of the current practice of concomitant use of coronary angiography and IVUS is that the locations of the acquired IVUS images are not correlated with their exact locations on the vessel roadmap obtained by coronary angiography. METHODS: Phantoms simulating the coronary tree were used to test the accuracy and potential of co-registration. Subsequently we examined patients who underwent IVUS during cardiac catheterization. Analysis and feasibility were performed in 42 arteries of 36 patients. RESULTS: The statistical validation in phantoms resulted in a co-registration accuracy of 1.12 mm. The length measurement on an angiogram resulted in an accuracy of 0.38 mm. Co-registration in patients was successful in all cases and four categories were assisted by 1(bad) to 5 (good) grading. Accuracy (the co-registration precision in pointing at the exact corresponding location): 4.8±0.41; Ease of use and workflow: 4.74±0.44; Stent landing zone detection and evaluation: 4.58±0.5; Stent landing zone length and diameter measurement: 4.94±0.23. The co-registration error was estimated as no more than 1 mm. CONCLUSION: In this pilot study, we found that the novel IVUS and coronary angiography co-registration method is accurate, easy to use, fast and user-friendly. This method precludes the need to use motorized automated pull back device.

Derivation of baseline lung impedance in chronic heart failure patients: use for monitoring pulmonary congestion and predicting admissions for decompensation.

The instantaneous lung impedance (ILI) is one of the methods to assess pulmonary congestion or edema (PCE) in chronic heart failure (CHF) patients. Due to usually existing PCE in CHF patients when evaluated, baseline lung impedance (BLI) is unknown. Therefore, the relation of ILI to BLI is unknown. Our aim was to evaluate methods to calculate and appraise BLI or its derivative as reflecting the clinical status of CHF patients. ILI and New York Heart Association (NYHA) class were assessed in 222 patients (67 ± 11 years, LVEF <35 %) during 32 months of frequent outpatient clinic visits. ILI, measured in 120 asymptomatic patients at NYHA class I, with no congestion on the chest X-ray and a low-normal 6-min walk, was defined as BLI. Using measured BLI and ILI values in these patients, formulas for BLI calculation were derived based on logistic regression analysis or on the disparity between BLI and ILI values at different NYHA stages. Both models were equally reliable with <3 % difference between measured and calculated BLI (p = NS). ΔLIR = (ILI/BLI - 1) × 100 % reflected the degree of PCE, or deviation from baseline, correlated with NYHA class (r = -0.9, p < 0.001) and could serve for monitoring. Of study patients, 123 were re-hospitalized for PCE during follow up. Their ΔLIR decreased gradually from -21.7 ± 8.2 % 4 weeks pre-admission to -37.8 ± 9.3 % on admission (p < 0.001). Patients improved during hospital stay (NYHA 3.7 ± 0.5 to 2.9 ± 0.8, p < 0.0001) with ΔLIR increasing to -29.1 ± 12.0 % (p < 0.001). ΔLIR based on calculated BLI correlated with the clinical status of CHF patients and allowed the prediction of hospitalizations for PCE.

Novel acute collateral flow index in patients with total coronary artery occlusion during ST-elevation myocardial infarction.

BACKGROUND: The effect of collaterals to occluded coronary arteries during ST-elevation myocardial infarction (STEMI) is unclear. The conventional CVP-based formula to calculate collateral flow index during STEMI yields values higher than in elective patients, which prompted derivation of a modified formula, pertinent in STEMI when left ventricular mean diastolic pressure (LVMDP) is the extravascular pressure limiting collateral flow. We aimed to evaluate this new LVMDP-based acute collateral flow index (ACFI). METHODS AND RESULTS: The pressure distal to coronary artery occlusion (P(d)) was measured during intervention in 111 consecutive STEMI patients, 67 (61%) of whom underwent primary intervention, followed for 58 months. ACFI (0.18 ± 0.17, median 0.15) correlated with both P(d) and collateral grade (P<0.0001). Higher creatine kinase levels and white cell counts were measured in the lowest ACFI tertile compared with the highest tertile group (P<0.012). ACFI correlated slightly with early regional but not with global left ventricular ejection fraction or with long-term coronary events and mortality. CONCLUSIONS: The ACFI is appropriate for evaluating collateral function during STEMI. Collateral flow during STEMI may marginally limit myocardial damage but had no effect on left ventricular contraction or long-term mortality, most likely because of the low flow provided by emerging collaterals and the high proportion of patients undergoing intervention before the beneficial effect of collaterals could be realized.

Impact of the Admission Pathway on the Gender-Related Mortality of Patients With ST-Elevation Myocardial Infarction.

The mortality of women with ST-elevation myocardial infarction (STEMI) exceeds that of men, supposedly the result of older age and co-morbidities. Patients with STEMI can be transported directly to the catherization lab by the emergency medical service (EMS) or to the emergency department (ED) by the EMS, a regular ambulance, or independently. This raises the question whether gender disparity in the transport of patients with STEMI may affect time to therapy and consequently explain the disparate outcome in men and women with STEMI. We analyzed a large nationwide registry of prospectively-recorded patients with acute coronary syndromes in order to determine if there is a survival gap between men and women with STEMI, and to assess the gender-related effect of admission pathway on time intervals and 5-year mortality. Study population included 2,740 patients with STEMI who underwent primary percutaneous coronary interventions, comprising 464 women (17%, median-70 years) and 2,276 men (83%, median-58 years). The unadjusted 5-year mortality of women was higher compared with men (26.4% vs 15.6%, p = 0.001) but adjustment abrogated this survival difference. Regardless of adjustment, the 5-year mortality of patients with STEMI admitted directly to the catherization lab or to the ED by EMS was similar for men and women but significantly lower in the directly admitted patients (p <0.028). In contrast, admission to the ED by non-EMS was associated with markedly worse survival among women. These results indicate that women suspected of STEMI benefit from transportation by the EMS and should use this pathway exclusively to reach the hospital.

Atrial fibrillation and long-term prognosis in patients hospitalized for heart failure: results from heart failure survey in Israel (HFSIS).

AIMS: Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and each adversely affects the other. The aim of the study was to prospectively evaluate the impact of AF and its subtypes on management, and early and long-term outcome of hospitalized HF patients. METHODS AND RESULTS: Data were prospectively collected on HF patients hospitalized in all public hospitals in Israel as part of a national survey (HFSIS). Atrial fibrillation patients were subdivided into intermittent and chronic AF subgroups. During March-April 2003, we enrolled 4102 HF patients, of whom 1360 (33.2%) had AF [600 (44.1%) intermittent, 562 (41.3%) chronic]. Patients with AF were older (76.9 +/- 10.5 vs. 71.7 +/- 12.6 years, P = 0.0001), males, with preserved LV systolic function. Crude mortality rates for AF patients were progressively and consistently higher during hospitalization and during the 4-year follow-up period, especially in the chronic AF group (P = 0.0001). After covariate adjustment, AF was associated with increased 1-year mortality [HR 1.19, 95% CI (1.03-1.36)]. CONCLUSION: AF was present in a third of hospitalized HF patients, and identified a population with increased mortality risk, largely due to co-morbidities.

Direct Admission of Patients With ST-Segment-Elevation Myocardial Infarction to the Catheterization Laboratory Shortens Pain-to-Balloon and Door-to-Balloon Time Intervals but Only the Pain-to-Balloon Interval Impacts Short- and Long-Term Mortality.

Background Shortening the pain-to-balloon (P2B) and door-to-balloon (D2B) intervals in patients with ST-segment-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) is essential in order to limit myocardial damage. We investigated whether direct admission of PPCI-treated patients with STEMI to the catheterization laboratory, bypassing the emergency department, expedites reperfusion and improves prognosis. Methods and Results Consecutive PPCI-treated patients with STEMI included in the ACSIS (Acute Coronary Syndrome in Israel Survey), a prospective nationwide multicenter registry, were divided into patients admitted directly or via the emergency department. The impact of the P2B and D2B intervals on mortality was compared between groups by logistic regression and propensity score matching. Of the 4839 PPCI-treated patients with STEMI, 1174 were admitted directly and 3665 via the emergency department. Respective median P2B and D2B were shorter among the directly admitted patients with STEMI (160 and 35 minutes) compared with those admitted via the emergency department (210 and 75 minutes, P<0.001). Decreased mortality was observed with direct admission at 1 and 2 years and at the end of follow-up (median 6.4 years, P<0.001). Survival advantage persisted after adjustment by logistic regression and propensity matching. P2B, but not D2B, impacted survival (P<0.001). Conclusions Direct admission of PPCI-treated patients with STEMI decreased mortality by shortening P2B and D2B intervals considerably. However, P2B, but not D2B, impacted mortality. It seems that the D2B interval has reached its limit of effect. Thus, all efforts should be extended to shorten P2B by educating the public to activate early the emergency medical services to bypass the emergency department and allow timely PPCI for the best outcome.

Differentiation between myopericarditis and acute myocardial infarction on presentation in the emergency department using the admission C-reactive protein to troponin ratio.

BACKGROUND: The treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy. METHODS: We evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients. RESULTS: Median admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p<0.001) demonstrating good differentiating capability. The Receiver-operator-curve of admission CRP/troponin ratio for diagnosis of myopericarditis against all AMI, STEMI, and NSTEMI patients yielded an area-under-the curve of 0.74, 0.73, and 0.765, respectively. CRP/troponin ratio>500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%. CONCLUSION: The CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation.

Collateral pressure and flow in acute myocardial infarction with total coronary occlusion correlate with angiographic collateral grade and creatine kinase levels.

BACKGROUND: The validity of angiographic collateral grade according to the Rentrop classification during acute myocardial infarction (AMI) and its relation to flow in occluded coronary arteries before angioplasty have never been evaluated. METHODS: We assessed the validity of the angiographic collateral grade according to Rentrop classification in relation to collateral pressure and flow beyond occluded coronary arteries during AMI. Pressure distal to coronary artery occlusions before balloon dilatation was measured in 111 patients undergoing angioplasty for AMI. We calculated the collateral flow index (CFI) and compared it to observed Rentrop grade and measured creatine kinase sum. RESULTS: The values of pressure distal to coronary artery occlusions with respect to collateral grades 0 to 3 were 33 +/- 12, 37 +/- 13, 42 +/- 10, and 60 +/- 14 mm Hg (P < .0001). Overall CFI was 0.35 +/- 0.13 (median 0.33), with CFI values of 0.3 +/- 0.13, 0.33 +/- 0.13, 0.39 +/- 0.1, and 0.57 +/- 0.2 for collateral grades 0 to 3, respectively (P < .0001). Larger creatine kinase elevation (P < .016) and higher white blood cell count (P < .022) were recorded in the lowest tertile CFI compared with highest tertile CFI group; but no difference in the global, regional, or infarct-related regional left ventricular contraction was found. CONCLUSIONS: These observations demonstrate that the Rentrop classification is valid in AMI patients with occluded coronary arteries and that collaterals are recruited acutely. These collaterals, whose pressure-derived CFI during AMI was shown for the first time to be higher than its value reported in chronic conditions, may limit the immediate myocardial damage or the systemic inflammatory response. No impact on global or regional cardiac contraction was detected in a population where most patients were treated early.

Acute diagonal-induced ST-elevation myocardial infarction and electrocardiogram-guidance in the era of primary coronary intervention: New insights into an old tool.

BACKGROUND: Previous studies, published before the advent of primary reperfusion, described the electrocardiographic features of ST-segment elevation myocardial infarction (STEMI) caused by total diagonal artery occlusion, as demonstrated at pre-discharge coronary angiography. We aimed to assess the electrocardiographic and echocardiographic features in STEMI unequivocally attributed to a diagonal lesion in the era of primary coronary intervention. METHODS: The electrocardiograms and echocardiograms of patients sustaining STEMI caused by diagonal artery involvement were compared with those of patients with STEMI attributed to proximal or mid left anterior descending artery (LAD) lesions. ST-segment deviations were measured at four different points in each lead and analyzed against TIMI flow and SNuH score. The electrocardiographic and echocardiographic features of each group were mapped. RESULTS: In contrast to previous studies claiming an ever-present incidence of at least 1-mm ST-segment elevation in leads I and aVL with diagonal STEMI, we report 86% of any ST-elevation in leads I, aVL and V2 (64-71% for ST-elevation >1 mm). Both higher SNuH score and pre-intervention TIMI flow were associated with larger lateral ST-elevations (85.7% and 86.4-95.5%, respectively). Higher prevalence of ST-depression in the inferior leads reflecting reciprocal changes was observed in patients with diagonal-induced STEMI (57-76% vs. 24-51% in LAD obstructions, p <0.05). CONCLUSION: The most sensitive and predictive sign for acute ischemia was any degree of ST-deviation measured 1 mm beyond the J point. ST-elevations in I, aVL and V2, sparing V3-V5, strongly favor isolated diagonal lesion. Proximal LAD lesion lacking ST-segment elevations in leads I and aVL is primarily due to wraparound LAD anatomy.

Optimal Timing for Coronary Intervention in Patients With Transient ST-Elevation Myocardial Infarction.

STEMI patients admitted urgently to the hospital but experience early complete resolution of both ischemic symptoms and ST-elevations on the electrocardiogram are diagnosed as transient STEMI (TSTEMI). Current evidence indicates that primary intervention is plausible but in certain circumstances intervention can be delayed. We sought to examine whether there is a time limit to such a delay that may affect long-term outcome. Study population included prospectively admitted TSTEMI patients whose demographics, pertinent medical history, and clinical and angiographic features were recorded. Study patients were divided by the median time interval from admission to intervention and their characteristics and long-term survival were compared. Study population comprised 260 consecutive patients (age: 57±10 years, men: 84%) diagnosed as TSTEMI who were included from January 2000 to June 2019, which represent 6% of all STEMI patients. Coronary angiography was performed in 254 patients. The median time interval from admission to angiography was 17 hours (IQR: 7.2 to 38.7 hours). Early (<17 hours from admission) and late (>17 hours from admission) study groups were comparable. One patient died during admission and 41 throughout the long follow-up period of 8.5 ± 5.2 years (median: 8.2 years, IQR: 3.4 to 13.1). Mortality of early-treated TSTEMI patients (11.2%) was significantly lower than of the late-treated patients (21.6%, p <0.04). The Kaplan-Meier curve demonstrated a clear tendency toward improved survival in early-treated TSTEMI patients (p <0.09). In conclusion, the present data suggest that TSTEMI patients should be treated, if not by primary coronary intervention, then at least within 17 hours from admission to achieve better long-term outcome.

Transient ST-elevation myocardial infarction: clinical course with intense medical therapy and early invasive approach, and comparison with persistent ST-elevation myocardial infarction.

Patients presenting with ST-elevation myocardial infarction (STEMI), whose symptoms and electrocardiographic changes completely resolve upon admission and before the administration of reperfusion therapy, pose a therapeutic dilemma. The optimal management of this syndrome, termed here as transient STEMI (TSTEMI), has not yet been fully determined. We describe 69 prospectively recorded patients with TSTEMI, of which 63 patients (56.7 +/- 11 years, 48 men) were available for long-term follow-up out of 1244 consecutive patients with acute myocardial infarction (5%). Patients with TSTEMI treated with intravenous isosorbide dinitrate, aspirin, and clopidogrel, and/or with glycoprotein IIb/IIIa inhibitors were compared with a control group of matched patients with STEMI without resolution, who were treated conventionally. The time interval from symptom onset to presentation at the emergency department of patients with TSTEMI was 1.7 +/- 1.3 hours, and to first recording of ST elevations, 1.5 +/- 1.4 hours. Symptoms and electrocardiographic changes fully resolved 1.2 +/- 0.8 hours later, 1 hour after aspirin and nitrate administration. Coronary angiography, performed 36 +/- 39 hours (median, 24 hours) from admission, demonstrated no obstructive lesion or single-vessel obstructive disease in 43 patients (70%). Primary coronary intervention was performed in 48 patients (77%), and 8 patients (13%) were referred to surgery. Left ventricular ejection fraction was within normal limits, and peak creatine kinase was mildly elevated. Patients with TSTEMI had less extensive coronary artery disease (P < .038), better thrombolysis in myocardial infarction flow on angiography (P < .01), lower peak creatine kinase level (P < .001), higher left ventricular ejection fraction (P < .0001), and lower likelihood to sustain a second additional coronary event after index admission (P = .024) than patients with STEMI. Transient STEMI was associated with less myocardial damage, less extensive coronary artery disease, higher thrombolysis in myocardial infarction flow grade in culprit artery, and better cardiac function. These data suggest that immediate intense medical therapy with an early invasive approach is an appropriate therapy in patients with TSTEMI.

B-type natriuretic peptide-guided therapy for heart failure (HF): a systematic review and meta-analysis of individual participant data (IPD) and aggregate data.

BACKGROUND: We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). METHODS: Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. RESULTS: We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53-0.92, patients < 75 years old and HR 1.07, 95% CI 0.84-1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71-0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83-2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). CONCLUSION: BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013005335.

Prediction of readmissions and mortality in patients with heart failure: lessons from the IMPEDANCE-HF extended trial.

AIMS: Readmissions for heart failure (HF) are a major burden. We aimed to assess whether the extent of improvement in pulmonary fluid content (ΔPC) during HF hospitalization evaluated by lung impedance (LI), or indirectly by other clinical and laboratory parameters, predicts readmissions. METHODS AND RESULTS: The present study is based on pre-defined secondary analysis of the IMPEDANCE-HF extended trial comprising 266 HF patients at New York Heart Association Class II-IV and left ventricular ejection fraction ≤ 35% randomized to LI-guided or conventional therapy during long-term follow-up. Lung impedance-guided patients were followed for 58 ± 36 months and the control patients for 46 ± 34 months (P < 0.01) accounting for 253 and 478 HF hospitalizations, respectively (P < 0.01). Lung impedance, N-terminal pro-brain natriuretic peptide, weight, radiological score, New York Heart Association class, lung rales, leg oedema, or jugular venous pressure were measured at admission and discharge on each hospitalization in both groups with the difference defined as ΔPC. Average LI-assessed ΔPC was 12.1% vs. 9.2%, and time to HF readmission was 659 vs. 306 days in the LI-guided and control groups, respectively (P < 0.01). Lung impedance-based ΔPC predicted 30 and 90 day HF readmission better than ΔPC assessed by the other variables (P < 0.01). The readmission rate for HF was lower if ΔPC > median compared with ΔPC ≤ median for all parameters evaluated in both study groups with the most pronounced difference predicted by LI (P < 0.01). Net reclassification improvement analysis showed that adding LI to the traditional clinical and laboratory parameters improved the predictive power significantly. CONCLUSIONS: The extent of ΔPC improvement, primarily the LI based, during HF-hospitalization, and study group allocation strongly predicted readmission and event-free survival time.

Characteristics, Management, and Outcome of Transient ST-elevation Versus Persistent ST-elevation and Non-ST-elevation Myocardial Infarction.

Patients with acute myocardial infarctions (AMIs) present as persistent ST-elevation myocardial infarction (STEMI) or as non-ST-segment elevation myocardial infarction (NSTEMI). In some patients with STEMI, ST elevations are transient and resolve before coronary intervention (transient ST-elevation myocardial infarction [TSTEMI]). We analyzed our registry comprising all consecutive patients with AMI admitted during 2009 to 2014, and compared the characteristics, management, and outcome of patients with TSTEMI with those of patients with STEMI and NSTEMI. Of 1,847 patients with AMI included in the registry, 1,073 patients sustained a STEMI (58%), 649 had a NSTEMI (35%), and 126 presented with TSTEMI (6.9%). Patients with TSTEMI were younger than patients with NSTEMI and STEMI (56.5 vs 62.8, p <0.001, and 59.5 years, p <0.02, respectively), smoked more (77.8 vs 54.0, p <0.001, and 62.1%, p <0.0005), and fewer were hypertensive (52.4 vs 74.2% and 58.8%, both p <0.001) and diabetic (26.2% vs 47.7%, p <0.0001, and 36.9%, p <0.02). The extent of coronary artery disease in patients with TSTEMI was similar to that of patients with STEMI except for less involvement of the left anterior descending artery (p <0.001), but less extensive than in NSTEMI patients. TSTEMI involved less myocardial damage by troponin-T level (p <0.005) with better cardiac function (LVEF 61% vs 55% and 49%, both p <0.0001). Mortality was lower among TSTEMI both in-hospital (0 vs 2.3% [p = NS] and 4.2% [p <0.01]) and long-term (4.8% vs 14.7% and 14.2%, both p <0.003) at a median of 36 months. In conclusion, TSTEMI is an acute coronary syndrome distinct from NSTEMI and STEMI, characterized by fewer risk factors, a similar extent of coronary artery disease to STEMI, but is associated with less myocardial damage and portends a better outcome.