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Acute Heart Failure With and Without Concomitant Acute Coronary Syndromes: Patient Characteristics, Management, and Survival
Journal of Cardiac Failure Vol. 20 No. 10 2014
Acute Heart Failure With and Without Concomitant Acute Coronary Syndromes: Patient Characteristics, Management, and Survival € TUUKKA TARVASMAKI, MD,1 VELI-PEKKA HARJOLA, MD, PhD,2 MARKKU S. NIEMINEN, MD, PhD,3 3 € KRISTA SIIRILA-WARIS, MD, JUKKA TOLONEN, MD, PhD,1 HELI TOLPPANEN, MD,3 AND JOHAN LASSUS, MD, PhD,3 FOR THE FINN-AKVA STUDY GROUP Helsinki, Finland
ABSTRACT Background: Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Methods and Results: Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs 43%; P ! .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P ! .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P ! .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs 8%; P 5 .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07e3.79; P 5 .03). Conclusions: Whereas medical history and the manifestation and initial treatment of AHF between ACSAHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. (J Cardiac Fail 2014;20:723e730) Key Words: Acute heart failure, acute coronary syndromes, management, survival.
Acute heart failure (AHF) is an important reason for hospitalization in Western countries and is associated with poor prognosis. Coronary artery disease (CAD) is a major cause of heart failure (HF),1 and acute coronary syndromes (ACS)
are the precipitating factor in up to one-third of AHF cases.2e4 Data suggest that AHF patients may have a worse prognosis when they have CAD, concomitant ischemia, or both.5e7 Regarding treatment of concomitant ACS, AHF guidelines mainly emphasize the importance of coronary angiography and revascularization.1,8,9 Overall, patients presenting with AHF have much higher mortality rates than ACS patients.10 Increased short- and long-term mortality is associated with concomitant HF in the setting of unstable angina pectoris (UAP) or myocardial infarction (MI).11e14 In addition, data suggest that compared with ACS patients without HF, ACS patients with complicating HF are less likely to receive the recommended therapies.11e14 Of note, ACS patients have often been excluded from AHF trials, leaving characteristics and treatment of AHF precipitated by ACS (ACS-AHF) inadequately described. In the present study, we evaluated ACS-AHF patients compared with AHF patients with no concomitant ACS (nACS-AHF) regarding clinical profile, management, and survival.
From the 1Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; 2Division of Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland and 3Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland. Manuscript received January 27, 2014; revised manuscript received June 29, 2014; revised manuscript accepted July 16, 2014. Reprint requests: Tuukka Tarvasm€aki, MD, Department of Medicine, Helsinki University Central Hospital, PO Box 372, 00029 HUS, Helsinki, Finland. Tel: þ358 40 534 3955; Fax: þ358 9 471 71488. E-mail: tuukka. [email protected] Funding: FINN-AKVA was supported by grants from the Paulo Foundation (Helsinki, Finland), the Finnish Foundation for Cardiovascular Research (Helsinki, Finland), and an unrestricted grant from Orion Pharma (Espoo, Finland). See page 729 for disclosure information. 1071-9164/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2014.07.008
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724 Journal of Cardiac Failure Vol. 20 No. 10 October 2014 Methods The Finnish Acute Heart Failure Study (FINN-AKVA) prospectively enrolled 620 consecutive patients hospitalized for AHF in 14 Finnish hospitals during 3 months in 2004.4 Inclusion in the study required confirmation of an AHF diagnosis during the hospital stay. The study included patients with de novo (new-onset) AHF and those with exacerbation of chronic HF. Patients were enrolled only once in the study, and data on their medical history, clinical presentation, and initial management were recorded in detail. Oral medication was registered both on admission and at discharge. On the basis of clinical presentation, patients were classified according to the ESC 2005 guideline classification into 5 groups15,16: 1. Cardiogenic shock (CS): evidence of tissue hypoperfusion (eg, oliguria) and low blood pressure (systolic blood pressure !90 mm Hg or need for vasopressors to maintain perfusion) caused by HF after correction of preload. 2. Pulmonary edema: acute heart failure with severe respiratory distress, crackles on lung auscultation, and pulmonary edema on chest x-ray, usually with O2 saturation !90% on room air. 3. Acute decompensated HF: signs and symptoms of AHF not fulfilling the criteria of hypertensive crisis, pulmonary edema, or CS. 4. Hypertensive AHF: Signs and symptoms of AHF accompanied by high blood pressure (O160 mm Hg) and relatively preserved left ventricular function (ejection fraction O40%) with congestion or pulmonary edema on chest radiograph. 5. Right HF: AHF predominantly due to right ventricular failure. Signs and symptoms of decreased cardiac output, distension of jugular veins, enlarged liver, and severe edema. Our study did not include patients with high-output HF. All patients gave their written informed consents. FINN-AKVA was approved by local Ethics Committees and was conducted in concordance with the Declaration of Helsinki. We investigated characteristics at presentation, initial management, and long-term survival of ACS-AHF and nACS-AHF patients as a secondary analysis of the FINN-AKVA cohort. Investigators at each participating center assessed factors causing AHF (UAP, MI, infection, arrhythmias) for each patient. ACS was defined as UAP or MI. Troponin T (TnT) levels were measured with the use of a Roche Elecsys 2010 assay on admission and at the 48-hour time point. The cutoff value for elevated TnT was 0.03 mg/L. Initial treatment included intravenous (IV) medication such as nitrates, furosemide, opioids, inotropes (levosimendan or dobutamine), and vasopressors (dopamine, noradrenaline, or adrenaline) as well as noninvasive ventilation (NIV) within the first 48 hours after admission. Invasive diagnostic and therapeutic coronary procedures (angiography, percutaneous coronary intervention [PCI], and coronary artery bypass graft surgery [CABG]) were recorded during the index hospitalization. In addition, we compared the doses of beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and spironolactone at discharge with recommended target doses.1 Documentation included length of stay (LOS) as well as admissions to cardiac (CCU) and intensive (ICU) care units. All-cause mortality was determined for all patients up to 5 years after the index hospitalization from the national Population Register Center, as was the time of death.
Statistical analyses were with the use of SPSS 21 statistical software (IBM Corp, Armonk, New York), with results presented as numbers and percentages, mean with standard deviation, or median with interquartile range for variables not normally distributed. We used the c2 test for comparison of categoric variables, the t test and Mann-Whitney U test for continuous variables, and the Kaplan-Meier method for survival analyses, and we compared survival between groups with the use of the log-rank test. To evaluate the independent effect of ACS on mortality, we performed multivariable logistic regression, adjusting for potential confounders, including sex, age, medical history (previous history of HF, CAD, hypertension, diabetes, cerebrovascular disease, and chronic obstructive pulmonary disease) as well as systolic blood pressure, anemia (defined as hemoglobin !120 g/L for women and !130 g/L for men), hyponatremia (sodium !135 mmol/L), and estimated glomerular filtration rate (calculated with the use of the CKD-EPI equation) on admission. Odds ratios (ORs) are shown with 95% confidence intervals (CIs). We considered P values of !.05 to be statistically significant.
Results Patients’ mean age was 75 6 10 years; one-half were women. ACS was a precipitating factor for 32% of patients, and of these only 39% had a history of HF; thus, most ACS-AHF presented as de novo AHF. As presented in Table 1, ACS-AHF patients more frequently had a history of CAD, MI, diabetes, or hypercholesterolemia. The clinical presentation of CS and pulmonary edema was more frequent among ACS-AHF patients, but at presentation no major differences existed between these groups overall in parameters or in biochemistry, apart from TnT and N-terminal proeB-type natriuretic peptide (Table 1). ACS-AHF patients received IV treatments and NIV more often (Table 2). IV furosemide was the most common treatment in both groups, given to as many as 85% of ACS-AHF patients. IV nitrate was frequent in ACS-AHF (69%); in contrast, fewer than one-third of nACS-AHF patients received it. A striking difference appeared in the use of inotropes and vasopressors, with a 5-fold greater use of the latter in ACS-AHF. In addition, NIV use was twice as common in nACS-AHF. Invasive coronary procedures differed markedly between the groups. In ACS-AHF, coronary angiography and revascularization (PCI/CABG) during the index hospitalization were more frequent (Table 2). A rather large proportion of revascularized ACS-AHF patients underwent CABG (38%). Although 43% of nACS-AHF patients had elevated TnT levels, only 8% of them underwent an angiography; revascularization rates also were very low. ACS-AHF patients were more frequently admitted to a CCU or an ICU and had longer LOS (Table 2). Prescription of cardiac medications increased during hospitalization in both groups (Fig. 1). Before hospitalization, ACS-AHF patients more frequently received lipid-lowering agents and antithrombotics, whereas furosemide, spironolactone, and warfarin were more common among nACSAHF patients. No difference existed between the groups
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Table 1. Study Population and Characteristics Between the Groups All n (%) Age (y) Women Medical history Previous heart failure Coronary artery disease Previous myocardial infarct Chronic atrial fibrillation/flutter Valvular disease Hypertension Cerebrovascular disease Diabetes COPD Peripheral artery disease Hypercholesterolemia Clinical class Cardiogenic shock Pulmonary edema ADHF Right heart failure Hypertensive AHF Clinical presentation Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm) LVEF (%; n 5 410) Hemoglobin (g/L) Sodium (mmol/L) CRP (g/L) eGFR (mL min1 1.73 m2) NT-proBNP (pg/mL; n 5 326) Elevated TnT (n 5 394)
ACS-AHF
nACS-AHF
P Value
620 75 6 10 307 (50)
198 (32) 76 6 9 106 (54)
422 (68) 75 6 11 201 (48)
316 342 172 167 83 339 108 200 78 63 159
(51) (55) (28) (27) (13) (55) (17) (32) (13) (10) (26)
77 138 78 26 25 117 38 79 17 27 74
(39) (70) (39) (13) (13) (59) (19) (40) (9) (14) (37)
239 204 94 141 58 222 70 121 61 34 85
(57) (48) (22) (34) (14) (53) (17) (29) (15) (9) (20)
!.001 !.001 !.001 !.001 .703 .130 .425 .005 .040 .050 !.001
14 163 394 30 19
(2) (26) (64) (5) (3)
9 83 98 3 5
(5) (42) (50) (2) (3)
5 80 296 27 14
(1) (19) (70) (6) (3)
.009 !.001 !.001 .008 .594
147 6 33 82 6 20 91 6 27 45 6 16 127 6 18 138 6 5 10 (3e26) 56 6 21 5,627 (2,605e11,373) 237 (60)
148 6 33 82 6 21 91 6 25 45 6 15 128 6 18 138 6 5 54 (40e67) 55 6 21 6,946 (2,971e13,306) 130 (91)
147 6 33 83 6 19 91 6 28 45 6 17 127 6 18 138 6 5 56 (42e72) 57 6 22 2,548 (5,363e10,333) 107 (43)
.099 .170
.582 .706 .849 .913 .372 .202 .760 .330 .128 !.001
ACS-AHF, acute heart failure with concomitant acute coronary syndrome; ADHF, acute decompensated heart failure; AHF, acute heart failure; BP, blood pressure; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate (calculated with the use of CKD-EPI equation); HR, heart rate; nACS-AHF, acute heart failure without concomitant acute coronary syndrome; NTproBNP, N-terminal proeB-type natriuretic peptide; TnT, troponin T. Results for categoric variables are presented as n (%) and continuous variables as mean 6 SD or median (interquartile range).
in BB or ACEi/ARB use on admission or at discharge (Fig. 1). In addition, we found no significant differences at discharge between the groups in their dosages of BBs or ACEi/ARBs in relation to dosages recommended by the guidelines1 (Table 3). At discharge, continuation of furosemide and spironolactone was more common for nACS-AHF.
Overall, cumulative 30-day mortality was 9%, and during 1 year of follow-up 28% of the total study population died. In-hospital mortality was significantly higher for ACS-AHF (12% vs 5%; P 5 .002). Although 30-day mortality was significantly higher among ACS-AHF patients (13% vs 8%; P 5 .027), long-term mortality was similar: 29% vs 27% (P 5 .5) at 1 year, and 59% vs 61% (P 5 .6) at 5 years for
Table 2. Initial AHF Treatments and Invasive Coronary Procedures, Length of Stay, and Admissions to Cardiac and Intensive Care Units in the Groups, n (%) Initial Treatment
All
ACS-AHF
nACS-AHF
IV nitrate 258 IV furosemide 470 IV opioid 179 Inotrope 33 Vasopressor 46 NIV 150 Invasive coronary procedures during hospitalization Coronary angiography 102 PCI 32 CABG 24 Length of stay and admissions to CCU/ICU Length of stay, median (IQR) 7 Admitted to CCU 245 Admitted to ICU 74
(42) (76) (29) (5) (7) (24)
136 168 97 22 32 76
122 302 82 11 14 74
(17) (5) (4) (5e11) (40) (12)
(69) (85) (49) (11) (16) (38)
69 (35) 31 (16) 20 (10) 8 (6e13) 120 (61) 43 (22)
P Value
(29) (72) (19) (3) (3) (18)
!.001 !.001 !.001 !.001 !.001 !.001
33 (8) 1 (0.2) 4 (1)
!.001 !.001 !.001
7 (5e10) 125 (30) 31 (7)
.003 !.001 !.001
CABG, coronary artery bypass graft; CCU, cardiac care unit; ICU, intensive care unit; IQR, interquartile range; IV, intravenous; NIV, noninvasive ventilation; PCI, percutaneous coronary intervention; other abbreviations as in Table 1.
726 Journal of Cardiac Failure Vol. 20 No. 10 October 2014
Fig. 1. Proportion of patients with cardiovascular medication (A) on admission and (B) at discharge. *P ! .01; **P ! .001 for comparison between ACS-AHF and nACS-AHF. ACEi, angiotensin-converting enzyme inhibitor; ACS-AHF, acute heart failure with concomitant acute coronary syndrome; ARB, angiotensin receptor blocker; ASA, aspirin; nACS-AHF, acute heart failure without concomitant acute coronary syndrome.
ACS-AHF and nACS-AHF, respectively (Fig. 2). In fact, ACS was an independent predictor of prognosis at 30 days in multivariable analysis (adjusted OR 2.0, 95% CI 1.07e3.79; P 5 .03), but not at 1 year (adjusted OR 1.0, 95% CI 0.66e1.58; P 5 .9), or at 5 years (adjusted OR 0.89, 95% CI 0.6e1.4; P 5 .6). Because the majority of ACS patients had actual MI (146/198), we repeated the analyses excluding UAP patients and choosing MI as the precipitating factor, Table 3. Doses of Medications at Discharge in Relation to Recommended Target Doses (%, mean 6 SD) Medication Beta-blocker ACE inhibitor ARB Spironolactone
All 53 63 37 87
6 6 6 6
ACS-AHF 27 31 21 22
50 64 40 83
6 6 6 6
26 30 26 24
nACS-AHF
P Value
6 6 6 6
.085 .798 .527 .362
55 63 36 88
28 32 21 21
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; other abbreviations as in Table 1.
obtaining similar results: indeed, concomitant MI was associated with increased 30-day mortality (adjusted OR 2.4, 95% CI 1.25e4.72; P 5 .009), but had no significant effect on long-term mortality (1-y adjusted OR 1.3, 95% CI 0.8e2.1 [P 5 .4]; 5-y adjusted OR 1.0, 95% CI 0.6e1.7 [P 5 .9]). Because patients with CS experience high mortality rates, and most of these patients had ACS, we repeated the multivariable analysis with exclusion of CS patients; ACS still remained an independent predictor of prognosis at 30 days (adjusted OR 1.9, 95% CI 1.01e3.73; P 5 .047). Likewise, when we excluded ICU patients from the analysis, the effect of ACS at 30 days remained similar (adjusted OR 2.5, 95% CI 1.08e5.67; P 5 .03). Discussion Our examination here of differences in characteristics, initial management, and survival between ACS-AHF and
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Fig. 2. Kaplan-Meier survival curves after admission to hospital due to AHF with (dashed line) and without (solid line) concomitant ACS. The vertical dashed lines indicate 30-day and 12-month time points. The inset figure represents the difference in 30-day survival. Abbreviations as in Fig. 1.
nACS-AHF patients is among very few studies describing the clinical presentation and real-life management of patients with ACS as the factor precipitating AHF. In addition, no data compare long-term survival between ACSAHF and nACS-AHF. In our study, clinical presentation in ACS-AHF was more severe. A strong association appeared between concomitant ACS and all of the therapies. Strikingly, IV furosemide, inotropes, and vasopressors were even more common than was predictable from clinical manifestations, with a high proportion of de novo AHF and low rates of CS. Long-term outcome was similar, but at 30 days ACS-AHF patients showed significantly poorer survival. Regarding CCU/ICU admission frequency, LOS, and short-term survival, concomitant ACS seemed to result in a more severe manifestation of AHF. Interestingly, no significant differences appeared in clinical variables such as baseline heart rate, blood pressure, or routine biochemistry. Nevertheless, considering the distribution of clinical classes of AHF, the acuteness of ACS-AHF does seem greater. What is noteworthy is that the higher proportion of CS and ICU admissions with ACS-AHF failed, however, to explain the difference in short-term mortality. When we used only actual MI as the precipitating factor of AHF in
the analyses, survival remained similar, thus confirming the effect of an ischemic event on short-term mortality. In-hospital mortality seems to account for poor shortterm survival for ACS-AHF, whereasdas in the Euroheart Failure Survey II2dpost-discharge survival between these groups is somewhat similar. Because the majority of ACS-AHF patients present as de novo AHF cases, changes in cardiac function and increases in left ventricular filling pressures are more abrupt than in most nACS-AHF patients. At the same time, treatment of the causative factor, ie, ischemia, may translate into fewer long-term sequelae and less chronic HF. We earlier reported that a history of chronic HF is a major determinant of long-term mortality.17 It is therefore worth noting that even with a higher proportion of de novo AHF, ACS-AHF patients had a 5-year mortality similar to that of patients with nACS-AHF. The clinical importance of the increased early mortality for ACS-AHF cannot be overlooked. Regarding the difference in short-term survival, it is noteworthy that no differences arose in the use of prognostically beneficial AHF medications (BB and ACEi/ARB). The nACS-AHF patients had already received spironolactone more frequently on admission, and this difference remained similar at discharge.
728 Journal of Cardiac Failure Vol. 20 No. 10 October 2014 AHF and ST-segment elevation MI guidelines provide similar recommendations for AHF treatment,1,18 the mainstay of which are diuretics, vasodilators, and ventilatory support. ACS-AHF patients more frequently received IV furosemide, though, especially in the setting of de novo AHF, ACS is not likely to be associated with fluid retention, but rather with pulmonary congestion due to left ventricular failure. Although ACS patients logically received IV nitrates and opioids more often due to their more severe manifestation of AHF, these medications are assimilated into treatment for ischemia and chest pain rather than of congestion and dyspnea. IV nitrate for nACS-AHF, especially, was strikingly low. While conclusive data on survival benefit are unavailable,19 guidelines still recommend use of a vasodilators,1,8,9 which, compared with other standard acute-phase medications, have a low incidence of adverse effects and may overall be more beneficial in AHF.19e22 In addition, vasodilators as a part of management strategy are currently a topic of active research. Need for ventilatory support is most likely associated with severity of respiratory distress and with a higher proportion of pulmonary edema in ACS-AHF. Although the proportion of CS in both groups was small, the difference in inotrope and vasopressor use was striking. The higher proportion of pulmonary edema may, in part, account for this difference, because data suggest that indeed pulmonary edema patients do receive these medications, even without marked hypotension.16,23 Considering that inotropes and vasopressors have been associated with worse outcome in AHF,24e26 their seemingly liberal use is alarming. Moreover, they may be particularly harmful in AHF patients with ischemic heart disease.25,27e29 Consequently, to avoid unnecessary harm and worsened outcomes, especially in ACS-AHF, inotropes and vasopressors should be used only after careful consideration. In part, the greater acuteness of ACS-AHF seems to explain some of the differences in guidelinerecommended AHF treatments. In studies comparing ACS patients with and without concomitant HF, the latter were, however, more likely to receive the recommended cardiac medications.11,12,14 Considering our results, we think that ACS per se is, to some extent, affecting management strategy. Although data suggest that early revascularization improves outcomes,30 ACS-AHF patients underwent invasive coronary procedures at a relatively low frequency. Moreover, despite the absence of evident ongoing ischemia or angina pectoris, CAD may cause stunning or hibernation of myocardium, thus leading to LV dysfunction that is possible to correct with revascularization.31 In addition, coronary angiography seems to lead to increased application of the appropriate cardiac medications.32 Unfortunately, frequency of invasive coronary procedures in AHF has proven to be suboptimal at best,6,11,12,30,33e35 and illogically, ACS patients even seem to undergo these procedures more frequently when they show no concomitant HF.11e13
In part, the low rate of invasive coronary procedures may be related to differences in local practice, and possibly some patients were considered to be unsuitable for such interventions. Additionally, because most ACS-AHF patients had a history of CAD, it is possible that their coronary anatomy was already known, so that no subsequent invasive procedures were considered necessary. Also, FINN-AKVA included centers with no on-site angiography facilities. Although such centers were a minority, this may have, in part, affected the low use of angiography and revascularization. Although the availability of coronary angiography has improved since the FINN-AKVA study, it was already then a common practice to perform it on patients with ACS. One Finnish study showed that one-half of its patients with noneST-segment elevation ACS underwent angiography in 2003.36 In any case, it is quite possible that higher rates of early revascularization would have improved the ACS-AHF patients’ short-term survival. Some limitations need acknowledgement. First, local investigators assessed the diagnosis of ACS based on contemporary guidelines; the diagnosis did not, however, undergo adjudication. Because symptoms and findings of ACS (chest discomfort/pain, electrocardiographic changes, troponin elevation) overlap with those of AHF, under- or overdiagnosis of ACS may have occurred. TnT values in the present study were analyzed centrally from collected blood samples, whereas the local investigators used locally analyzed troponin values. Although troponin elevation occurs in AHF without actual ACS, it is still associated with worse outcome.25,29 Second, even though the time frame regarding analysis of IV medication and NIV use was limited to the first 48 hours after hospitalization, we feel that this time frame defines the initial management appropriately. We also believe that the differences in clinical presentation and characteristics of ACS-AHF and nACS-AHF probably have so far remained mostly unchanged. Conclusion Compared with nACS-AHF patients, ACS-AHF patients more often present with de novo HF and have a more severe clinical manifestation of AHF. Consequently, the 2 groups differed in terms of initial treatment of AHF: ACS-AHF patients receive IV medications and coronary procedures more often. Nevertheless, although no significant differences appeared in our patients’ long-term survival, LOS was longer and 30-day mortality higher in ACS-AHF. Thus, further research is essential into the management of ACS-AHF patients; this important population should not be excluded from future randomized clinical trials. FINN-AKVA Study Group: V.-P. Harjola, K. Siiril€aWaris, Nieminen, Helsinki University Central Hospital; J. Melin, Central Finland Central Hospital; K. Peuhkurinen, Kuopio University Hospital; M. Halkosaari, KeskiPohjanmaa Central Hospital; K. H€anninen, Kymenlaakso Central Hospital; T. Ilva, T. Talvensaari, Kanta-H€ame
AHF With and Without Concomitant ACS
Central Hospital; H. Kervinen, Hyvink€a€a Hospital; K. Kiilavuori, Jorvi Hospital; K. Majamaa-Voltti, Oulu University Hospital; H. M€akynen, V. Virtanen, Tampere University Hospital; T. Salmela-Mattila, Rauma Hospital; K. Soininen, Kuusankoski Hospital; M. Strandberg, H. Ukkonen, Turku University Hospital; I. Vehmanen, Turku Hospital; E.-P. Sandell, Espoo, Finland. Study nurses: K. Hautakoski, Keski-Pohjanmaa Central Hospital; J. Lamminen, Hyvink€a€a Hospital; M.-L. Niskanen, Kuopio University Hospital; M. Pietil€a, Helsinki University Central Hospital; O. Surakka, Central Finland Central Hospital. Disclosures None.
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12. Steg PG, Dabbous OH, Feldman LJ, Cohen-Solal A, Aumont MC, Lopez-Sendon J, et al. Determinants and prognostic impact of heart failure complicating acute coronary syndromes: observations from the Global Registry of Acute Coronary Events (GRACE). Circulation 2004;109:494e9. 13. Haim M, Battler A, Behar S, Fioretti PM, Boyko V, Simoons ML, et al. Acute coronary syndromes complicated by symptomatic and asymptomatic heart failure: does current treatment comply with guidelines? Am Heart J 2004;147:859e64. 14. Roe MT, Chen AY, Riba AL, Goswami RG, Peacock WF, Pollack CV Jr, et al. Impact of congestive heart failure in patients with noneST-segment elevation acute coronary syndromes. Am J Cardiol 2006;97:1707e12. 15. Nieminen MS, Bohm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G, et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J 2005;26:384e416. 16. Tarvasmaki T, Harjola VP, Tolonen J, Siirila-Waris K, Nieminen MS, Lassus J, et al. Management of acute heart failure and the effect of systolic blood pressure on the use of intravenous therapies. Eur Heart J Acute Cardiovasc Care 2013;2:219e25. 17. Lassus JP, Siirila-Waris K, Nieminen MS, Tolonen J, Tarvasmaki T, Peuhkurinen K, et al. Long-term survival after hospitalization for acute heart failuredDifferences in prognosis of acutely decompensated chronic and new-onset acute heart failure. Int J Cardiol 2013; 168:458e62. 18. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, et al, Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology (ESC). ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33: 2569e619. 19. Wakai A, McCabe A, Kidney R, Brooks SC, Seupaul RA, Diercks DB, et al. Nitrates for acute heart failure syndromes. Cochrane Database Syst Rev 2013;8:CD005151. 20. Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, et al. Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med 2011; 37:290e301. 21. Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz A, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet 1998;351:389e93. 22. Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, et al. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol 2008;52:200e7. 23. Parissis JT, Nikolaou M, Mebazaa A, Ikonomidis I, Delgado J, VilasBoas F, et al. Acute pulmonary oedema: clinical characteristics, prognostic factors, and in-hospital management. Eur J Heart Fail 2010;12: 1193e202. 24. Elkayam U, Tasissa G, Binanay C, Stevenson LW, Gheorghiade M, Warnica JW, et al. Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure. Am Heart J 2007; 153:98e104. 25. Felker GM, Benza RL, Chandler AB, Leimberger JD, Cuffe MS, Califf RM, et al. Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 2003;41:997e1003. 26. Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 2005;46: 57e64.
730 Journal of Cardiac Failure Vol. 20 No. 10 October 2014 27. Schulz R, Rose J, Martin C, Brodde OE, Heusch G. Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation. Circulation 1993;88: 684e95. 28. Indolfi C, Piscione F, Perrone-Filardi P, Prastaro M, Di Lorenzo E, Sacca L, et al. Inotropic stimulation by dobutamine increases left ventricular regional function at the expense of metabolism in hibernating myocardium. Am Heart J 1996;132:542e9. 29. Peacock WF 4th, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS, et al. Cardiac troponin and outcome in acute heart failure. N Engl J Med 2008;358:2117e26. 30. Flaherty JD, Rossi JS, Fonarow GC, Nunez E, Stough WG, Abraham WT, et al. Influence of coronary angiography on the utilization of therapies in patients with acute heart failure syndromes: findings from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF). Am Heart J 2009;157:1018e25. 31. Camici PG, Rimoldi OE. The contribution of hibernation to heart failure. Ann Med 2004;36:440e7. 32. Steg PG, Kerner A, van de Werf F, Lopez-Sendon J, Gore JM, Fitzgerald G, et al. Impact of in-hospital revascularization on survival
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in patients with noneST-elevation acute coronary syndrome and congestive heart failure. Circulation 2008;118:1163e71. Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005;149:209e16. Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, et al. Euroheart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J 2006;27:2725e36. Oliva F, Mortara A, Cacciatore G, Chinaglia A, Di Lenarda A, Gorini M, et al. Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian Registry on Heart Failure Outcome. Eur J Heart Fail 2012;14:1208e17. Vikman S, Airaksinen KE, Tierala I, Peuhkurinen K, MajamaaVoltti K, Niemela M, et al. Improved adherence to practice guidelines yields better outcome in high-risk patients with acute coronary syndrome without ST elevation: findings from nationwide FINACS studies. J Intern Med 2004;256:316e23.
Acute Heart Failure With and Without Concomitant Acute Coronary Syndromes: Patient Characteristics, Management, and Survival € TUUKKA TARVASMAKI, MD,1 VELI-PEKKA HARJOLA, MD, PhD,2 MARKKU S. NIEMINEN, MD, PhD,3 3 € KRISTA SIIRILA-WARIS, MD, JUKKA TOLONEN, MD, PhD,1 HELI TOLPPANEN, MD,3 AND JOHAN LASSUS, MD, PhD,3 FOR THE FINN-AKVA STUDY GROUP Helsinki, Finland
ABSTRACT Background: Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Methods and Results: Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs 43%; P ! .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P ! .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P ! .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs 8%; P 5 .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07e3.79; P 5 .03). Conclusions: Whereas medical history and the manifestation and initial treatment of AHF between ACSAHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. (J Cardiac Fail 2014;20:723e730) Key Words: Acute heart failure, acute coronary syndromes, management, survival.
Acute heart failure (AHF) is an important reason for hospitalization in Western countries and is associated with poor prognosis. Coronary artery disease (CAD) is a major cause of heart failure (HF),1 and acute coronary syndromes (ACS)
are the precipitating factor in up to one-third of AHF cases.2e4 Data suggest that AHF patients may have a worse prognosis when they have CAD, concomitant ischemia, or both.5e7 Regarding treatment of concomitant ACS, AHF guidelines mainly emphasize the importance of coronary angiography and revascularization.1,8,9 Overall, patients presenting with AHF have much higher mortality rates than ACS patients.10 Increased short- and long-term mortality is associated with concomitant HF in the setting of unstable angina pectoris (UAP) or myocardial infarction (MI).11e14 In addition, data suggest that compared with ACS patients without HF, ACS patients with complicating HF are less likely to receive the recommended therapies.11e14 Of note, ACS patients have often been excluded from AHF trials, leaving characteristics and treatment of AHF precipitated by ACS (ACS-AHF) inadequately described. In the present study, we evaluated ACS-AHF patients compared with AHF patients with no concomitant ACS (nACS-AHF) regarding clinical profile, management, and survival.
From the 1Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; 2Division of Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland and 3Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland. Manuscript received January 27, 2014; revised manuscript received June 29, 2014; revised manuscript accepted July 16, 2014. Reprint requests: Tuukka Tarvasm€aki, MD, Department of Medicine, Helsinki University Central Hospital, PO Box 372, 00029 HUS, Helsinki, Finland. Tel: þ358 40 534 3955; Fax: þ358 9 471 71488. E-mail: tuukka. [email protected] Funding: FINN-AKVA was supported by grants from the Paulo Foundation (Helsinki, Finland), the Finnish Foundation for Cardiovascular Research (Helsinki, Finland), and an unrestricted grant from Orion Pharma (Espoo, Finland). See page 729 for disclosure information. 1071-9164/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2014.07.008
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724 Journal of Cardiac Failure Vol. 20 No. 10 October 2014 Methods The Finnish Acute Heart Failure Study (FINN-AKVA) prospectively enrolled 620 consecutive patients hospitalized for AHF in 14 Finnish hospitals during 3 months in 2004.4 Inclusion in the study required confirmation of an AHF diagnosis during the hospital stay. The study included patients with de novo (new-onset) AHF and those with exacerbation of chronic HF. Patients were enrolled only once in the study, and data on their medical history, clinical presentation, and initial management were recorded in detail. Oral medication was registered both on admission and at discharge. On the basis of clinical presentation, patients were classified according to the ESC 2005 guideline classification into 5 groups15,16: 1. Cardiogenic shock (CS): evidence of tissue hypoperfusion (eg, oliguria) and low blood pressure (systolic blood pressure !90 mm Hg or need for vasopressors to maintain perfusion) caused by HF after correction of preload. 2. Pulmonary edema: acute heart failure with severe respiratory distress, crackles on lung auscultation, and pulmonary edema on chest x-ray, usually with O2 saturation !90% on room air. 3. Acute decompensated HF: signs and symptoms of AHF not fulfilling the criteria of hypertensive crisis, pulmonary edema, or CS. 4. Hypertensive AHF: Signs and symptoms of AHF accompanied by high blood pressure (O160 mm Hg) and relatively preserved left ventricular function (ejection fraction O40%) with congestion or pulmonary edema on chest radiograph. 5. Right HF: AHF predominantly due to right ventricular failure. Signs and symptoms of decreased cardiac output, distension of jugular veins, enlarged liver, and severe edema. Our study did not include patients with high-output HF. All patients gave their written informed consents. FINN-AKVA was approved by local Ethics Committees and was conducted in concordance with the Declaration of Helsinki. We investigated characteristics at presentation, initial management, and long-term survival of ACS-AHF and nACS-AHF patients as a secondary analysis of the FINN-AKVA cohort. Investigators at each participating center assessed factors causing AHF (UAP, MI, infection, arrhythmias) for each patient. ACS was defined as UAP or MI. Troponin T (TnT) levels were measured with the use of a Roche Elecsys 2010 assay on admission and at the 48-hour time point. The cutoff value for elevated TnT was 0.03 mg/L. Initial treatment included intravenous (IV) medication such as nitrates, furosemide, opioids, inotropes (levosimendan or dobutamine), and vasopressors (dopamine, noradrenaline, or adrenaline) as well as noninvasive ventilation (NIV) within the first 48 hours after admission. Invasive diagnostic and therapeutic coronary procedures (angiography, percutaneous coronary intervention [PCI], and coronary artery bypass graft surgery [CABG]) were recorded during the index hospitalization. In addition, we compared the doses of beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and spironolactone at discharge with recommended target doses.1 Documentation included length of stay (LOS) as well as admissions to cardiac (CCU) and intensive (ICU) care units. All-cause mortality was determined for all patients up to 5 years after the index hospitalization from the national Population Register Center, as was the time of death.
Statistical analyses were with the use of SPSS 21 statistical software (IBM Corp, Armonk, New York), with results presented as numbers and percentages, mean with standard deviation, or median with interquartile range for variables not normally distributed. We used the c2 test for comparison of categoric variables, the t test and Mann-Whitney U test for continuous variables, and the Kaplan-Meier method for survival analyses, and we compared survival between groups with the use of the log-rank test. To evaluate the independent effect of ACS on mortality, we performed multivariable logistic regression, adjusting for potential confounders, including sex, age, medical history (previous history of HF, CAD, hypertension, diabetes, cerebrovascular disease, and chronic obstructive pulmonary disease) as well as systolic blood pressure, anemia (defined as hemoglobin !120 g/L for women and !130 g/L for men), hyponatremia (sodium !135 mmol/L), and estimated glomerular filtration rate (calculated with the use of the CKD-EPI equation) on admission. Odds ratios (ORs) are shown with 95% confidence intervals (CIs). We considered P values of !.05 to be statistically significant.
Results Patients’ mean age was 75 6 10 years; one-half were women. ACS was a precipitating factor for 32% of patients, and of these only 39% had a history of HF; thus, most ACS-AHF presented as de novo AHF. As presented in Table 1, ACS-AHF patients more frequently had a history of CAD, MI, diabetes, or hypercholesterolemia. The clinical presentation of CS and pulmonary edema was more frequent among ACS-AHF patients, but at presentation no major differences existed between these groups overall in parameters or in biochemistry, apart from TnT and N-terminal proeB-type natriuretic peptide (Table 1). ACS-AHF patients received IV treatments and NIV more often (Table 2). IV furosemide was the most common treatment in both groups, given to as many as 85% of ACS-AHF patients. IV nitrate was frequent in ACS-AHF (69%); in contrast, fewer than one-third of nACS-AHF patients received it. A striking difference appeared in the use of inotropes and vasopressors, with a 5-fold greater use of the latter in ACS-AHF. In addition, NIV use was twice as common in nACS-AHF. Invasive coronary procedures differed markedly between the groups. In ACS-AHF, coronary angiography and revascularization (PCI/CABG) during the index hospitalization were more frequent (Table 2). A rather large proportion of revascularized ACS-AHF patients underwent CABG (38%). Although 43% of nACS-AHF patients had elevated TnT levels, only 8% of them underwent an angiography; revascularization rates also were very low. ACS-AHF patients were more frequently admitted to a CCU or an ICU and had longer LOS (Table 2). Prescription of cardiac medications increased during hospitalization in both groups (Fig. 1). Before hospitalization, ACS-AHF patients more frequently received lipid-lowering agents and antithrombotics, whereas furosemide, spironolactone, and warfarin were more common among nACSAHF patients. No difference existed between the groups
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Table 1. Study Population and Characteristics Between the Groups All n (%) Age (y) Women Medical history Previous heart failure Coronary artery disease Previous myocardial infarct Chronic atrial fibrillation/flutter Valvular disease Hypertension Cerebrovascular disease Diabetes COPD Peripheral artery disease Hypercholesterolemia Clinical class Cardiogenic shock Pulmonary edema ADHF Right heart failure Hypertensive AHF Clinical presentation Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm) LVEF (%; n 5 410) Hemoglobin (g/L) Sodium (mmol/L) CRP (g/L) eGFR (mL min1 1.73 m2) NT-proBNP (pg/mL; n 5 326) Elevated TnT (n 5 394)
ACS-AHF
nACS-AHF
P Value
620 75 6 10 307 (50)
198 (32) 76 6 9 106 (54)
422 (68) 75 6 11 201 (48)
316 342 172 167 83 339 108 200 78 63 159
(51) (55) (28) (27) (13) (55) (17) (32) (13) (10) (26)
77 138 78 26 25 117 38 79 17 27 74
(39) (70) (39) (13) (13) (59) (19) (40) (9) (14) (37)
239 204 94 141 58 222 70 121 61 34 85
(57) (48) (22) (34) (14) (53) (17) (29) (15) (9) (20)
!.001 !.001 !.001 !.001 .703 .130 .425 .005 .040 .050 !.001
14 163 394 30 19
(2) (26) (64) (5) (3)
9 83 98 3 5
(5) (42) (50) (2) (3)
5 80 296 27 14
(1) (19) (70) (6) (3)
.009 !.001 !.001 .008 .594
147 6 33 82 6 20 91 6 27 45 6 16 127 6 18 138 6 5 10 (3e26) 56 6 21 5,627 (2,605e11,373) 237 (60)
148 6 33 82 6 21 91 6 25 45 6 15 128 6 18 138 6 5 54 (40e67) 55 6 21 6,946 (2,971e13,306) 130 (91)
147 6 33 83 6 19 91 6 28 45 6 17 127 6 18 138 6 5 56 (42e72) 57 6 22 2,548 (5,363e10,333) 107 (43)
.099 .170
.582 .706 .849 .913 .372 .202 .760 .330 .128 !.001
ACS-AHF, acute heart failure with concomitant acute coronary syndrome; ADHF, acute decompensated heart failure; AHF, acute heart failure; BP, blood pressure; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate (calculated with the use of CKD-EPI equation); HR, heart rate; nACS-AHF, acute heart failure without concomitant acute coronary syndrome; NTproBNP, N-terminal proeB-type natriuretic peptide; TnT, troponin T. Results for categoric variables are presented as n (%) and continuous variables as mean 6 SD or median (interquartile range).
in BB or ACEi/ARB use on admission or at discharge (Fig. 1). In addition, we found no significant differences at discharge between the groups in their dosages of BBs or ACEi/ARBs in relation to dosages recommended by the guidelines1 (Table 3). At discharge, continuation of furosemide and spironolactone was more common for nACS-AHF.
Overall, cumulative 30-day mortality was 9%, and during 1 year of follow-up 28% of the total study population died. In-hospital mortality was significantly higher for ACS-AHF (12% vs 5%; P 5 .002). Although 30-day mortality was significantly higher among ACS-AHF patients (13% vs 8%; P 5 .027), long-term mortality was similar: 29% vs 27% (P 5 .5) at 1 year, and 59% vs 61% (P 5 .6) at 5 years for
Table 2. Initial AHF Treatments and Invasive Coronary Procedures, Length of Stay, and Admissions to Cardiac and Intensive Care Units in the Groups, n (%) Initial Treatment
All
ACS-AHF
nACS-AHF
IV nitrate 258 IV furosemide 470 IV opioid 179 Inotrope 33 Vasopressor 46 NIV 150 Invasive coronary procedures during hospitalization Coronary angiography 102 PCI 32 CABG 24 Length of stay and admissions to CCU/ICU Length of stay, median (IQR) 7 Admitted to CCU 245 Admitted to ICU 74
(42) (76) (29) (5) (7) (24)
136 168 97 22 32 76
122 302 82 11 14 74
(17) (5) (4) (5e11) (40) (12)
(69) (85) (49) (11) (16) (38)
69 (35) 31 (16) 20 (10) 8 (6e13) 120 (61) 43 (22)
P Value
(29) (72) (19) (3) (3) (18)
!.001 !.001 !.001 !.001 !.001 !.001
33 (8) 1 (0.2) 4 (1)
!.001 !.001 !.001
7 (5e10) 125 (30) 31 (7)
.003 !.001 !.001
CABG, coronary artery bypass graft; CCU, cardiac care unit; ICU, intensive care unit; IQR, interquartile range; IV, intravenous; NIV, noninvasive ventilation; PCI, percutaneous coronary intervention; other abbreviations as in Table 1.
726 Journal of Cardiac Failure Vol. 20 No. 10 October 2014
Fig. 1. Proportion of patients with cardiovascular medication (A) on admission and (B) at discharge. *P ! .01; **P ! .001 for comparison between ACS-AHF and nACS-AHF. ACEi, angiotensin-converting enzyme inhibitor; ACS-AHF, acute heart failure with concomitant acute coronary syndrome; ARB, angiotensin receptor blocker; ASA, aspirin; nACS-AHF, acute heart failure without concomitant acute coronary syndrome.
ACS-AHF and nACS-AHF, respectively (Fig. 2). In fact, ACS was an independent predictor of prognosis at 30 days in multivariable analysis (adjusted OR 2.0, 95% CI 1.07e3.79; P 5 .03), but not at 1 year (adjusted OR 1.0, 95% CI 0.66e1.58; P 5 .9), or at 5 years (adjusted OR 0.89, 95% CI 0.6e1.4; P 5 .6). Because the majority of ACS patients had actual MI (146/198), we repeated the analyses excluding UAP patients and choosing MI as the precipitating factor, Table 3. Doses of Medications at Discharge in Relation to Recommended Target Doses (%, mean 6 SD) Medication Beta-blocker ACE inhibitor ARB Spironolactone
All 53 63 37 87
6 6 6 6
ACS-AHF 27 31 21 22
50 64 40 83
6 6 6 6
26 30 26 24
nACS-AHF
P Value
6 6 6 6
.085 .798 .527 .362
55 63 36 88
28 32 21 21
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; other abbreviations as in Table 1.
obtaining similar results: indeed, concomitant MI was associated with increased 30-day mortality (adjusted OR 2.4, 95% CI 1.25e4.72; P 5 .009), but had no significant effect on long-term mortality (1-y adjusted OR 1.3, 95% CI 0.8e2.1 [P 5 .4]; 5-y adjusted OR 1.0, 95% CI 0.6e1.7 [P 5 .9]). Because patients with CS experience high mortality rates, and most of these patients had ACS, we repeated the multivariable analysis with exclusion of CS patients; ACS still remained an independent predictor of prognosis at 30 days (adjusted OR 1.9, 95% CI 1.01e3.73; P 5 .047). Likewise, when we excluded ICU patients from the analysis, the effect of ACS at 30 days remained similar (adjusted OR 2.5, 95% CI 1.08e5.67; P 5 .03). Discussion Our examination here of differences in characteristics, initial management, and survival between ACS-AHF and
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Fig. 2. Kaplan-Meier survival curves after admission to hospital due to AHF with (dashed line) and without (solid line) concomitant ACS. The vertical dashed lines indicate 30-day and 12-month time points. The inset figure represents the difference in 30-day survival. Abbreviations as in Fig. 1.
nACS-AHF patients is among very few studies describing the clinical presentation and real-life management of patients with ACS as the factor precipitating AHF. In addition, no data compare long-term survival between ACSAHF and nACS-AHF. In our study, clinical presentation in ACS-AHF was more severe. A strong association appeared between concomitant ACS and all of the therapies. Strikingly, IV furosemide, inotropes, and vasopressors were even more common than was predictable from clinical manifestations, with a high proportion of de novo AHF and low rates of CS. Long-term outcome was similar, but at 30 days ACS-AHF patients showed significantly poorer survival. Regarding CCU/ICU admission frequency, LOS, and short-term survival, concomitant ACS seemed to result in a more severe manifestation of AHF. Interestingly, no significant differences appeared in clinical variables such as baseline heart rate, blood pressure, or routine biochemistry. Nevertheless, considering the distribution of clinical classes of AHF, the acuteness of ACS-AHF does seem greater. What is noteworthy is that the higher proportion of CS and ICU admissions with ACS-AHF failed, however, to explain the difference in short-term mortality. When we used only actual MI as the precipitating factor of AHF in
the analyses, survival remained similar, thus confirming the effect of an ischemic event on short-term mortality. In-hospital mortality seems to account for poor shortterm survival for ACS-AHF, whereasdas in the Euroheart Failure Survey II2dpost-discharge survival between these groups is somewhat similar. Because the majority of ACS-AHF patients present as de novo AHF cases, changes in cardiac function and increases in left ventricular filling pressures are more abrupt than in most nACS-AHF patients. At the same time, treatment of the causative factor, ie, ischemia, may translate into fewer long-term sequelae and less chronic HF. We earlier reported that a history of chronic HF is a major determinant of long-term mortality.17 It is therefore worth noting that even with a higher proportion of de novo AHF, ACS-AHF patients had a 5-year mortality similar to that of patients with nACS-AHF. The clinical importance of the increased early mortality for ACS-AHF cannot be overlooked. Regarding the difference in short-term survival, it is noteworthy that no differences arose in the use of prognostically beneficial AHF medications (BB and ACEi/ARB). The nACS-AHF patients had already received spironolactone more frequently on admission, and this difference remained similar at discharge.
728 Journal of Cardiac Failure Vol. 20 No. 10 October 2014 AHF and ST-segment elevation MI guidelines provide similar recommendations for AHF treatment,1,18 the mainstay of which are diuretics, vasodilators, and ventilatory support. ACS-AHF patients more frequently received IV furosemide, though, especially in the setting of de novo AHF, ACS is not likely to be associated with fluid retention, but rather with pulmonary congestion due to left ventricular failure. Although ACS patients logically received IV nitrates and opioids more often due to their more severe manifestation of AHF, these medications are assimilated into treatment for ischemia and chest pain rather than of congestion and dyspnea. IV nitrate for nACS-AHF, especially, was strikingly low. While conclusive data on survival benefit are unavailable,19 guidelines still recommend use of a vasodilators,1,8,9 which, compared with other standard acute-phase medications, have a low incidence of adverse effects and may overall be more beneficial in AHF.19e22 In addition, vasodilators as a part of management strategy are currently a topic of active research. Need for ventilatory support is most likely associated with severity of respiratory distress and with a higher proportion of pulmonary edema in ACS-AHF. Although the proportion of CS in both groups was small, the difference in inotrope and vasopressor use was striking. The higher proportion of pulmonary edema may, in part, account for this difference, because data suggest that indeed pulmonary edema patients do receive these medications, even without marked hypotension.16,23 Considering that inotropes and vasopressors have been associated with worse outcome in AHF,24e26 their seemingly liberal use is alarming. Moreover, they may be particularly harmful in AHF patients with ischemic heart disease.25,27e29 Consequently, to avoid unnecessary harm and worsened outcomes, especially in ACS-AHF, inotropes and vasopressors should be used only after careful consideration. In part, the greater acuteness of ACS-AHF seems to explain some of the differences in guidelinerecommended AHF treatments. In studies comparing ACS patients with and without concomitant HF, the latter were, however, more likely to receive the recommended cardiac medications.11,12,14 Considering our results, we think that ACS per se is, to some extent, affecting management strategy. Although data suggest that early revascularization improves outcomes,30 ACS-AHF patients underwent invasive coronary procedures at a relatively low frequency. Moreover, despite the absence of evident ongoing ischemia or angina pectoris, CAD may cause stunning or hibernation of myocardium, thus leading to LV dysfunction that is possible to correct with revascularization.31 In addition, coronary angiography seems to lead to increased application of the appropriate cardiac medications.32 Unfortunately, frequency of invasive coronary procedures in AHF has proven to be suboptimal at best,6,11,12,30,33e35 and illogically, ACS patients even seem to undergo these procedures more frequently when they show no concomitant HF.11e13
In part, the low rate of invasive coronary procedures may be related to differences in local practice, and possibly some patients were considered to be unsuitable for such interventions. Additionally, because most ACS-AHF patients had a history of CAD, it is possible that their coronary anatomy was already known, so that no subsequent invasive procedures were considered necessary. Also, FINN-AKVA included centers with no on-site angiography facilities. Although such centers were a minority, this may have, in part, affected the low use of angiography and revascularization. Although the availability of coronary angiography has improved since the FINN-AKVA study, it was already then a common practice to perform it on patients with ACS. One Finnish study showed that one-half of its patients with noneST-segment elevation ACS underwent angiography in 2003.36 In any case, it is quite possible that higher rates of early revascularization would have improved the ACS-AHF patients’ short-term survival. Some limitations need acknowledgement. First, local investigators assessed the diagnosis of ACS based on contemporary guidelines; the diagnosis did not, however, undergo adjudication. Because symptoms and findings of ACS (chest discomfort/pain, electrocardiographic changes, troponin elevation) overlap with those of AHF, under- or overdiagnosis of ACS may have occurred. TnT values in the present study were analyzed centrally from collected blood samples, whereas the local investigators used locally analyzed troponin values. Although troponin elevation occurs in AHF without actual ACS, it is still associated with worse outcome.25,29 Second, even though the time frame regarding analysis of IV medication and NIV use was limited to the first 48 hours after hospitalization, we feel that this time frame defines the initial management appropriately. We also believe that the differences in clinical presentation and characteristics of ACS-AHF and nACS-AHF probably have so far remained mostly unchanged. Conclusion Compared with nACS-AHF patients, ACS-AHF patients more often present with de novo HF and have a more severe clinical manifestation of AHF. Consequently, the 2 groups differed in terms of initial treatment of AHF: ACS-AHF patients receive IV medications and coronary procedures more often. Nevertheless, although no significant differences appeared in our patients’ long-term survival, LOS was longer and 30-day mortality higher in ACS-AHF. Thus, further research is essential into the management of ACS-AHF patients; this important population should not be excluded from future randomized clinical trials. FINN-AKVA Study Group: V.-P. Harjola, K. Siiril€aWaris, Nieminen, Helsinki University Central Hospital; J. Melin, Central Finland Central Hospital; K. Peuhkurinen, Kuopio University Hospital; M. Halkosaari, KeskiPohjanmaa Central Hospital; K. H€anninen, Kymenlaakso Central Hospital; T. Ilva, T. Talvensaari, Kanta-H€ame
AHF With and Without Concomitant ACS
Central Hospital; H. Kervinen, Hyvink€a€a Hospital; K. Kiilavuori, Jorvi Hospital; K. Majamaa-Voltti, Oulu University Hospital; H. M€akynen, V. Virtanen, Tampere University Hospital; T. Salmela-Mattila, Rauma Hospital; K. Soininen, Kuusankoski Hospital; M. Strandberg, H. Ukkonen, Turku University Hospital; I. Vehmanen, Turku Hospital; E.-P. Sandell, Espoo, Finland. Study nurses: K. Hautakoski, Keski-Pohjanmaa Central Hospital; J. Lamminen, Hyvink€a€a Hospital; M.-L. Niskanen, Kuopio University Hospital; M. Pietil€a, Helsinki University Central Hospital; O. Surakka, Central Finland Central Hospital. Disclosures None.
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