Nonfatal Heart Failure Research Articles

Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the High-Risk-Myocardial-Infarction database

Abstract Background Sudden cardiac death (SCD) is responsible for 20–40% of mortality following acute myocardial infarction (AMI). The risk of SCD is even higher among patients with AMI complicated by heart failure (HF) (either clinically apparent HF or left ventricular dysfunction). The temporal relationship between an AMI complicated by HF and subsequent SCD and the association of non-fatal cardiovascular (CV) events following AMI with SCD has yet to be described. Purpose Among patients with AMI complicated by HF, we evaluated the probability and temporal association of subsequent non-fatal cardiovascular (CV) events (HF hospitalization, recurrent MI, or stroke) and SCD. Methods The High-Risk Myocardial Infarction (HRMI) database contains 28,771 patients with signs of HF or reduced LV ejection fraction (<40%) after AMI. Among patients with an AMI complicated by HF, we used adjudicated cause of death from the HRMI Database to identify: 1) the temporal distribution of SCD among patients following an index AMI; 2) the probability of having SCD following a non-fatal CV event following the index AMI. Results Median follow-up was 1.9 years. Mean age was 65.0±11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-year [py] and for SCD was 3.1 per 100py (40% of CV deaths). SCD rates were highest in the early period (<90 days) after AMI and decreased over time. Recurrent MI preceded 9.6% of SCD after a median time of 145 days; HF hospitalization preceded 17.0% of SCD after a median 144 days; and stroke preceded 2.7% of SCD after a median of 138 days (vs. non-sudden CV death: MI 46.6% at 1 days, HF hospitalization: 30.9% at 67 days, stroke 12.9% at 9 days). The incidence of SCD preceded by HF hospitalization was significantly higher than SCD without preceding HF hospitalization. Conclusion Among patients with AMI complicated by HF, SCD predominantly occurred in the early “high-risk” period after AMI; SCD rates decreased afterwards. Patients with non-fatal HF hospitalizations during follow-up may have a higher subsequent SCD risk. Preventing HF onset after MI may help decreasing SCD. Proportion of sudden cardiac death Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Lucien Award, McGill University

Association Between Obstructive Sleep Apnea-Hypopnea Syndrome and Outcomes in Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease.

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5–10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA.Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke.Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan–Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286–2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201–2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications.Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus.

BackgroundNT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) improves the discriminatory ability of risk‐prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT‐proBNP by itself for death and cardiovascular events in high‐risk patients with T2DM.Methods and ResultsCox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT‐proBNP alone and with NT‐proBNP added, using C‐statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6‐year follow‐up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT‐proBNP alone was as discriminatory as the base model for predicting death (C‐statistic, 0.745 versus 0.744, P=0.95) and the cardiovascular composite outcome (C‐statistic, 0.723 versus 0.731, P=0.37). When NT‐proBNP was added, it increased the predictive ability of the base model for death (C‐statistic, 0.779 versus 0.744, P<0.001) and for cardiovascular composite outcome (C‐statistic, 0.763 versus 0.731, P<0.001).ConclusionsIn high‐risk patients with T2DM, NT‐proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification.RegistrationURL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00549757.

Study design of Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS).

AimsThe role of non‐invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) (‘vulnerable phase’ HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse‐based follow‐up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face‐to‐face on‐site visits at the vulnerable post‐discharge phase.Methods and resultsWe designed a 24 week nationwide, multicentre, randomized, controlled, open‐label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non‐fatal HF events of a TM‐based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow‐up based on face‐to‐face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non‐fatal HF events (first and recurrent) at the end of a 6 month follow‐up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient‐reported outcomes.ConclusionsThe HERMeS trial will assess the efficacy of a TM‐based follow‐up strategy for real‐world ‘vulnerable phase’ HF patients combining telemonitoring and teleintervention.

SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials

Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. Boehringer Ingelheim.

Lifetime risk predictions for cardiovascular diseases: Competing risks analyses on a population-based cohort in Sweden

Background and aimsThere are guideline discussions on a lifetime approach to cardiovascular risk. Many of the available risk models estimate the short-term, usually 10-year risk of non-fatal and fatal cardiovascular diseases (CVD) grouped together. We aimed to develop lifetime risk models for non-fatal coronary heart disease, stroke, heart failure and death from CVD and non-CVD. MethodsWe included 92,915 individuals who had participated in a community-based lifestyle intervention programme at 40, 50 and/or 60 years of age. Their collected data on selected risk factors were linked to register data on hospitalizations and death. Parametric multivariable survival regression with a competing risks approach was employed to model cause-specific hazards, which were translated into cumulative incidence functions to provide the risk of experiencing each event separately. All analyses were performed gender-age wise. For illustrative purposes, “better” and “worse” risk profiles were created by setting three modifiable risk factors to the best and worst levels, respectively. ResultsMost of the risk factors qualified for inclusion in the regressions. Men had a higher risk of cardiovascular events and the events occurred at a younger age than women. In the created risk profiles, where serum total cholesterol, smoking status and blood pressure were modified, an excessive number of CVD events were observed in the worse profiles. ConclusionsUsing these models, the lifetime risk of each of the first CVD events can be estimated for different risk factor profiles. Since the predictions are diagnosis specific, the estimates are more accurate.

Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study

The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries. To assess the association of nuts with mortality and cardiovascular disease (CVD). The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35-70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure]. We followed 124,329 participants (age=50.7 y, SD=10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n=8,662) or major cardiovascular events (n=5,979)]. Higher nut intake (>120 g per wk compared with <30 g per mo) was associated with a lower risk of the primary composite outcome of mortality or major cardiovascular event [multivariate HR (mvHR): 0.88; 95% CI: 0.80, 0.96; P-trend=0.0048]. Significant reductions in total (mvHR: 0.77; 95% CI: 0.69, 0.87; P-trend<0.0001), cardiovascular (mvHR: 0.72; 95% CI: 0.56, 0.92; P-trend=0.048), and noncardiovascular mortality (mvHR: 0.82; 95% CI: 0.70, 0.96; P-trend=0.0046) with a trend to reduced cancer mortality (mvHR: 0.81; 95% CI: 0.65, 1.00; P-trend=0.081) were observed. No significant associations of nuts were seen with major CVD (mvHR: 0.91; 95% CI: 0.81, 1.02; P-trend=0.14), stroke (mvHR: 0.98; 95% CI: 0.84, 1.14; P-trend=0.76), or MI (mvHR: 0.86; 95% CI: 0.72, 1.04; P-trend=0.29). Higher nut intake was associated with lower mortality risk from both cardiovascular and noncardiovascular causes in low-, middle-, and high-income countries.

Characterisation of patients with and without cardiac magnetic resonance imaging abnormalities presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA)

Objective The objective of the current study is to determine the characteristics of myocardial infarction with non-obstructive coronary arteries (MINOCA) patients with and without cardiac magnetic resonance (CMR) abnormalities. Methods We evaluated patients admitted with a presentation of acute myocardial infarction (MI) with no coronary obstruction on invasive angiography in our institution between 2012 and 2017. Patients with prior cardiac disease, myocarditis, Takotsubo cardiomyopathy and type 2 myocardial infarction were excluded. Myocardial fibrosis was determined by late gadolinium enhancement (LGE). Patients were divided into two groups based on the presence or absence of CMR abnormalities (LGE or oedema). Major adverse cardiovascular events (MACE) were defined as non-fatal MI, all-cause mortality, ventricular arrythmias or heart failure hospitalisation at follow-up. Results Thirty-four patients fulfilling the inclusion criteria were identified. Myocardial changes with CMR were observed in 20 (59%) patients with signs of subendocardial infarct by LGE in 13 (38%) patients, transmural infarct by LGE in 6 (18%) patients and one patient had myocardial oedema. ECG and echocardiographic features were similar between patients with and without CMR abnormalities. Troponin T was significantly higher among patients with CMR abnormalities. The median duration of follow-up was 702 (IQR 456–1394) days. Two patients had MACE (both heart failure). One of them had LGE changes. Conclusions A significant number of patients with MINOCA have ischaemic LGE changes or myocardial wall oedema. The patients with CMR abnormalities have similar ECG and echocardiographic features except higher biomarker, highlighting the role of CMR in patients with MINOCA.

The importance of considering both primary and secondary diagnostic codes when using administrative health data to study acute coronary syndrome epidemiology (ANZACS-QI 47).

Routinely collected health administrative data have become an important data source for investigators assessing disease epidemiology. Our aim was to investigate the implications of identifying acute coronary syndrome (ACS) events in New Zealand (NZ) national hospitalization data using either the first (primary) or subsequent (secondary) codes. Using national health datasets, we identified all NZ hospitalizations (2014-16) for patients ≥20 years with a primary or secondary International Classification of Diseases 10th Revision, Australian Modification (ICD10-AM) ACS code. Outcomes included 1-year all-cause and cause-specific mortality, hospitalized non-fatal myocardial infarction, heart failure, stroke, or major bleeding, and a composite comprising these outcomes. Of 35 646 ACS hospitalizations, 78.5% were primary and 21.5% secondary diagnoses. Compared to primary coding, patients with a secondary diagnosis were older (mean 77 vs. 69 years), more likely to be females (48% vs. 36%), had more comorbidity, and were less likely to receive coronary angiography or revascularization. Higher adverse event rates were observed for the secondary diagnosis group including a three-fold higher 1-year mortality (40% vs. 13%) and two-fold higher composite adverse outcome (54% vs. 26%). The use of primary codes alone, rather than combined primary and secondary codes, resulted in overestimation of coronary angiography and revascularization rates, and underestimation of the 1-year case fatality (13.1% vs. 19.0%) and composite adverse event rate (26% vs. 32%). Patient characteristics and outcomes of ACS events recorded as primary vs. secondary codes are very different. These findings have important implications for designing studies utilizing ICD10-AM codes.

Cardiac Magnetic Resonance Feature Tracking Global Longitudinal Strain and Prognosis After Heart Transplantation

ObjectivesThis study determined the long-term prognostic significance of GLS assessed using CMR-FT in a large cohort of heart transplant recipients. BackgroundIn heart transplant recipients, global longitudinal strain (GLS) assessed using echocardiography has shown promise in the prediction of clinical outcomes. We hypothesized that CMR feature tracking (CMR-FT) GLS is independently associated with long-term outcomes in heart transplant recipients. MethodsIn a cohort of consecutive heart transplant recipients who underwent routine CMR for clinical surveillance, CMR-FT GLS was calculated from 3 long-axis cine CMR images. Associations between GLS and a composite endpoint of death or major adverse cardiac events (MACE), including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization, were investigated. ResultsA total of 152 heart transplant recipients (age 54 ± 15 years; 29% women; 5.0 ± 5.4 years after heart transplantation) were included. The median GLS was −11.6% (interquartile range: −13.6% to −9.2%). Over a median follow-up of 2.6 years, 59 recipients reached the composite endpoint. On Kaplan-Meier analyses, recipients with GLS worse than the median had a higher estimated cumulative incidence of the composite endpoint compared with recipients with GLS better than the median (log rank p = 0.004). On multivariate Cox proportional hazards regression, GLS was independently associated with the composite endpoint after adjustment for cardiac allograft vasculopathy, history of rejection, left ventricular ejection fraction (LVEF), right ventricular EF, and presence of myocardial fibrosis, with a hazard ratio of 1.15 for every 1% worsening in GLS (95% confidence interval: 1.06 to 1.24; p < 0.001). Similar results were seen in subgroups of recipients with LVEF >50% and with no myocardial fibrosis. GLS provided incremental prognostic value over other variables in the multivariate model as determined by the log-likelihood chi-squared test. ConclusionsIn a large cohort of heart transplant recipients, CMR-FT GLS was independently associated with the long-term risk of death or MACE.

The impact of antiplatelet therapy on patients with vasospastic angina: A multicenter registry study of the Japanese Coronary Spasm Association

BackgroundAntiplatelet therapy (APT) is generally used in patients with coronary artery disease. However, for patients with vasospastic angina (VSA), the impact of APT is not fully understood. MethodsIn a multicenter registry study of the Japanese Coronary Spasm Association (n = 1429), patients with or without APT were compared. The primary endpoint was major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, unstable angina, heart failure and appropriate ICD (Implantable cardioverter defibrillator) shock. Propensity score matching and a multivariable cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. ResultsIn the whole population, 669 patients received APT, while 760 patients did not receive APT. Patients with APT had a greater prevalence of comorbidities, such as hypertension, diabetes, dyslipidemia and smoking, than those without APT. The prevalences of previous myocardial infarction, spontaneous ST changes, significant organic stenosis and medications including calcium channel blocker, nitrate, statin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were greater in patients with APT than those without APT. After propensity matching (n = 335 for both groups), during the median follow-up period of 32 months, the incidence rate of MACE was comparable between the patients with and without APT (P = 0.24). MACEs occurred in 5.7% of patients with APT and in 3.6% of those without APT (P = 0.20). All-cause death occurred in 0.6% of patients with APT and 1.8% of those without APT (p = 0.16). ConclusionIn this multicenter registry study, anti-platelet therapy exerted no beneficial effects for VSA patients.

2-OR: Impact of N Terminal Pro B-Type Natriuretic Peptide and High Sensitivity Cardiac Troponin on the Prediction of Death and Cardiovascular Events in High-Risk Patients with Type 2 Diabetes

We assessed the relative contributions of N-terminal pro-B-type natriuretic peptide (NTBNP) and high sensitivity cardiac troponin (hsTnT) to the prediction of death and cardiovascular (CV) events in 5597 (with complete data) of 8561 patients with type 2 diabetes (T2DM) and CV disease (CVD) and/or chronic kidney disease (CKD) enrolled in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE). We analysed Harrell’s C-statistics (Cs) to estimate Cox model performance to predict death (n= 473) and a CV composite outcome (CVCO: CV death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke or heart failure hospitalization, n= 1129) after a median follow-up of 2.6 years, using a base model (BM) of 19 clinical baseline variables. The Cs for predicting death in the BM (0.724) was augmented by adding hsTnT (0.744, p= 0.002) which was further improved by NTBNP (0.779, p &amp;lt;0.001). Similarly, the BM for predicting CVCO Cs (0.716) was improved by hsTnT (0.732, p= 0.001) and enhanced further by including NTBNP in the model (0.763, p &amp;lt;0.001). Notably, NTBNP by itself was as predictive as BM plus hsTNT for predicting death (both 0.744, p= 1.0) and the CVCO (0.732 vs. 0.721, p= 0.27). In patients with T2DM and CVD or/and CKD, NTBNP was the major prognostic factor and should be considered for risk stratification. Disclosure M.V.B. Malachias: Speaker’s Bureau; Self; Biolab Sanus Farmaceutica, Libbs Farmaceutica. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. B. Claggett: None. M.O. Wijkman: None. R. Bentley-Lewis: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. P.C. Brunel: Consultant; Self; Novartis AG. N. Chaturvedi: Consultant; Self; AstraZeneca. A.S. Desai: Consultant; Self; Abbott, Alnylam Pharmaceuticals, AstraZeneca, Biofourmis, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, DalCor Pharmaceuticals, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Relypsa, Inc. Research Support; Self; Alnylam Pharmaceuticals, AstraZeneca, Novartis Pharmaceuticals Corporation. S.M. Haffner: None. H.D. Parving: None. M.F. Prescott: Employee; Self; Novartis Pharmaceuticals Corporation. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. M.A. Pfeffer: Consultant; Self; AstraZeneca, CinCor, Correvio, Corvidia, DalCor Pharmaceuticals, GlaxoSmithKline plc., Innovative Science, Jazz Pharmaceuticals, MyoKardia, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., PharmaScience, Sanofi US, Servier, Takeda Development Center Americas, Inc. Research Support; Self; Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals (NCT00549757)

Effect of Low Diastolic Blood Pressure to Cardiovascular Risk in Patients With Ischemic Stroke or Transient Ischemic Attacks Under Different Systolic Blood Pressure Levels.

Background: In the context of recently updated strategies of pressure management, there is a paucity of evidence on the effect of diastolic blood pressure (DBP) level on adverse events among stroke patients. This study aimed to examine the effect of low DBP (<60 mmHg) under different levels of systolic blood pressure (SBP) on the risk of composite events and stroke recurrence among patients with ischemic stroke (IS) or transient ischemic attack (TIA).Material and Methods: This study was conducted in 2,325 patients with IS or TIA. DBP values were categorized into <60, 60–70, 70–80 (reference), 80–90, and ≥90 mmHg in the main sample and were further categorized as <60 and ≥60 mmHg (reference) when patients were stratified according to SBP levels (<140, <130, and <120 mmHg). The outcomes were defined as recurrent stroke and cumulative composite events (defined as the combination of nonfatal myocardial infarction, nonfatal congestive heart failure, and death) at 1 year.Results: During 1 year of follow-up, a total of 95 composite events and 138 stroke recurrences were identified. The patients with low DBP showed a significantly higher risk of composite events [hazard ratio (HR) = 4.86, 95% confidence interval (CI) = 2.54–8.52], especially the elderly patients (≥60 years); however, this result was not observed for stroke recurrence (HR = 0.90, 95% CI = 0.46–1.74). With the reduction of the SBP levels, the proportion of patients with low DBP increased (6.87, 12.67, and 34.46%), and the risk for composite events persisted.Conclusions: Along with the new target levels of SBP suggested by updated criteria, there is a trend for DBP to be reduced to a harmfully low level, which was associated with an increased risk of composite events among patients with IS or TIA.

Risk of cardiovascular events in patients with metabolic syndrome: Results of a population-based prospective cohort study (PURE Turkey).

Objective:Metabolic syndrome (MetS) includes several cardiovascular (CV) risk factors. This study aimed to assess CV risk of MetS, contribution of its components to the risk, and whether MetS provides additional risk beyond its components.Methods:The Prospective Urban Rural Epidemiology (PURE) Turkey cohort included 3933 individuals aged between 35 and 70 years, with a median follow-up of 8.9 years. MetS was diagnosed as the presence of any of the following criteria: high blood pressure, high fasting plasma glucose, abdominal obesity, low HDL-cholesterol, or high triglycerides. The primary outcome was the composite of fatal CV events, non-fatal myocardial infarction, stroke or heart failure, adjusted for age, sex, smoking, family history of CV diseases, and LDL-cholesterol.Results:The primary outcome was more common in the MetS group [178 (9.2%) vs. 70 (3.5%); corresponding incidence rate of 11.3 vs. 4.2 per 1000 person-years; log-rank p<0.001]. Each component was significantly associated with the primary outcome; however, when the components were sequentially included in the model, abdominal obesity and high triglycerides did not provide additional risk on top of the other three components. The hazard ratio for MetS for the primary outcome was 2.12 (95% confidence interval 1.59–2.81, p<0.001), and the discriminative ability (c-statistics) of the models with MetS and the components was similar.Conclusion:MetS increases the risk of CV events more than two-fold. High blood pressure, high fasting plasma glucose, and low HDL-cholesterol are the top three components of MetS for CV risk. MetS and its components have a similar discriminative ability for CV events.

Myocardial Fibrosis and Prognosis in Heart Transplant Recipients.

Myocardial fibrosis is a well-described histopathologic feature in heart transplant recipients. Whether myocardial fibrosis in heart transplant recipients is independently associated with clinical outcomes is unclear. We sought to determine whether myocardial fibrosis on late gadolinium enhancement cardiovascular magnetic resonance imaging in heart transplant recipients was independently associated with all-cause death or major adverse cardiac outcomes in the long-term. Using a cohort of consecutive heart transplant recipients that had cardiovascular magnetic resonance imaging, we determined the prevalence and the patterns of myocardial fibrosis and analyzed associations between myocardial fibrosis and a composite end point of all-cause death or major adverse cardiac events: retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization. One hundred and fifty-two heart transplant recipients (age, 54±15 years; 29% women; 5.0±5.4 years after heart transplantation) were included. Myocardial fibrosis was present in 18% (37% infarct pattern, 41% noninfarct pattern, and 22% both). Its prevalence was positively associated with cardiac allograft vasculopathy grade. With a median follow-up of 2.6 years, myocardial fibrosis was independently associated with all-cause death or major adverse cardiac events (hazard ratio, 2.88; 95% CI, 1.59-5.23; P<0.001) after adjustment for cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume. Every 1% increase in myocardial fibrosis was independently associated with a 6% higher hazard for all-cause death or major adverse cardiac events (hazard ratio, 1.06; 95% CI, 1.03-1.09; P<0.001). The addition of myocardial fibrosis variables to models with cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume resulted in significant improvements in model fit, suggesting incremental prognostic value. In heart transplant recipients, myocardial fibrosis is seen on late gadolinium enhancement cardiovascular magnetic resonance imaging in 18%. Both the presence and the extent of myocardial fibrosis are independently associated with the long-term risk of all-cause death or major adverse cardiac events.

Improved long-term cardiovascular outcomes after intensive versus standard screening of diabetic complications: an observational study

BackgroundComplication screening is recommended for patients with type 2 diabetes (T2D), but the optimal screening intensity and schedules are unknown. In this study, we evaluated whether intensive versus standard complication screening affects long-term cardiovascular outcomes.MethodsIn this observational study, we included 368 T2D patients referred for intensive screening provided as a 1-day session of clinical–instrumental evaluation of diabetic complications, followed by dedicated counseling. From a total of 4906 patients, we selected control T2D patients who underwent standard complication screening at different visits, by 2:1 propensity score matching. The primary endpoint was the 4p-MACE, defined as cardiovascular mortality, or non-fatal myocardial infarction, stroke, or heart failure. The Cox proportional regression analyses was used to compare outcome occurrence in the two groups, adjusted for residual confounders.Results357 patients from the intensive screening group (out of 368) were matched with 683 patients in the standard screening group. Clinical characteristics were well balanced between the two groups, except for a slightly higher prevalence of microangiopathy in the intensive group (56% vs 50%; standardized mean difference 0.11, p = 0.1). Median follow-up was 5.6 years. The adjusted incidence of 4p-MACE was significantly lower in the intensive versus standard screening group (HR 0.70; 95% CI 0.52–0.95; p = 0.02). All components of the primary endpoint had nominally lower rates in the intensive versus standard screening group, which was particularly significant for heart failure (HR 0.43; 95% CI 0.22–0.83; p = 0.01).ConclusionAmong T2D patients attending a specialist outpatient clinic, intensive complication screening is followed by better long-term cardiovascular outcomes. No significant effect was noted for cardiovascular and all-cause mortality and the benefit was mainly driven by a reduced rate of hospitalization for heart failure.

Associations of Leisure-Time Physical Activity and Television Viewing With Life Expectancy Free of Nonfatal Cardiovascular Disease: The ARIC Study.

BackgroundHigh levels of physical activity have been associated with longer life expectancy free of cardiovascular disease (CVD), but specific types of CVD and sedentary behavior have not been examined. We examined associations of leisure‐time moderate‐to‐vigorous physical activity (LTPA) and television viewing with life expectancy free of 3 types of CVD.Methods and ResultsWe included 13 534 participants from the ARIC (Atherosclerosis Risk in Communities) cohort. We used multistate survival models to estimate associations of LTPA in the past year (no LTPA, less than the median, equal to or greater than the median) and television viewing (often or very often, sometimes, seldom or rarely) with life expectancy at age 50 free of nonfatal coronary heart disease (CHD), stroke, and heart failure (HF). Over 27 years of follow‐up, 4519 participants developed one of the 3 nonfatal CVDs and 5475 deaths occurred. Compared with participants who engaged in no LTPA, participants who engaged in LTPA equal to or greater than the median had longer life expectancy free of nonfatal CHD (men: 1.5 years [95% CI, 1.0–2.0]; women: 1.6 years [95% CI, 1.1–2.2]), stroke (men: 1.8 years [95% CI, 1.2–2.3]; women: 1.8 years [95% CI, 1.3–2.3]), and HF (men: 1.6 years [95% CI, 1.1–2.1]; women: 1.7 years [95% CI, 1.2–2.2]). Compared with viewing more television, watching less television was associated with longer life expectancy free of CHD, stroke, and HF (≈0.8 year).ConclusionsHigher levels of LTPA and less television viewing were associated with longer life expectancy free of CHD, stroke, and HF. Engaging in LTPA and watching less television may increase the number of years lived free of CHD, stroke, and HF.

Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes

Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. To evaluate the association of BP indexes with death and a composite CV event. Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors.

Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer. Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors. Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]). Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.

The VALID-CRT risk score reliably predicts response and outcome of cardiac resynchronization therapy in a real-world population.

ObjectivesThe aim of the study was to confirm the value of the VALID‐cardiac resynchronization therapy (CRT) risk score in predicting outcome and to assess its association with clinical response (CR) in an unselected real‐world CRT population.Methods and ResultsThe present analysis comprised all consecutive CRT patients (pts) enrolled in the CRT‐MORE registry from 2011 to 2013. Pts were stratified into five groups (quintiles 1‐5) according to the VALID‐CRT risk predictor index applied to the CRT‐MORE population. In the analysis of clinical outcome, adverse events comprised death from any cause and non‐fatal heart failure (HF) events requiring hospitalization. CR at 12‐month follow‐up was also assessed. We enrolled 905 pts. During a median follow‐up of 1005 [627‐1361] days, 134 patients died, and 79 had at least one HF hospitalization. At 12 months, 69% of pts displayed an improvement in their CR. The mean VALID‐CRT risk score derived from the CRT‐MOdular Registry (MORE) population was 0.317, ranging from −0.419 in Q1 to 2.59 in Q5. The risk‐stratification algorithm was able to predict total mortality after CRT (survival ranging from 93%‐Q1 to 77%‐Q5; hazards ratio [HR] = 1.42, 95% confidence interval [CI]: 1.25‐1.61, P < .0001), and HF hospitalization (ranging from 95% to 90%; HR = 1.24, 95% CI: 1.06‐1.45, P = .009). CR was significantly lower in pts with a high‐to‐very high risk profile (Q4‐5) than in pts with a low‐to‐intermediate risk profile (Q1‐2‐3) (55% vs 79%, P < .0001).ConclusionThe VALID‐CRT risk‐stratification algorithm reliably predicts outcome and CRT response after CRT in an unselected, real‐world population.