Non-cardiovascular Causes Of Death Research Articles

Trends in Isolated Mitral Valve Repair or Replacement Surgery in Australia: A Statewide Cohort Linkage Study

Global trends in mitral valve surgery (MVSx) suggest increasing repair compared with replacement, especially in the United States and European countries. The relative use, and outcomes of, MV repair and replacement in Australia are unknown. New South Wales residents who underwent isolated MVSx between 2001 and 2017 were identified from the Admitted-Patient-Data-Collection database. Mortality outcomes were tracked to 31 Dec 2018 and adjusted based on age, sex, urgency of operation, and comorbidity status. The study cohort comprised 5,693 patients: 2020 (35%) underwent repair (MVr), 1,656 (29%) underwent mechanical replacement (mech.MVR), and 2017 (35%) underwent bioprosthetic replacement (bio.MVR). Respective median ages [interquartile range] were 67 yo [59-75 yo], 64 yo [55-71 yo], and 75 yo [68-80 yo] (p<0.001 across groups). Between 2001 and 2017, total MVSx increased steadily with population growth. Whereas the relative use of MVr remained static (34% to 38%), that for bio.MVR (22% to 50%) and mech.MVR (45% to 13%) changed significantly. MVr had the best outcome with 1.2% in-hospital, 2.5% 1-year, and 21.6% total cumulative mortality during a median follow-up of 6.5 years. Compared to MVr, the adjusted hazard ratio (aHR) for mech.MVR and bio.MVR for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) and 1.73 (95% CI=1.53-1.95), respectively. Heart failure and sepsis were the main cardiovascular and noncardiovascular causes of death in all groups. In this statewide Australian cohort examined over 17 years, MVr is potentially underutilised despite having superior outcomes to MVR. Access to quality dataset which provides the indication for MVSx and quantitative clinical factors is critical to further improve MVr coverage and outcome MVSx.

Two-year outcomes of patients with atrial fibrillation treated with rivaroxaban: results from RIVER registry

Abstract Introduction Non-vitamin-K oral anticoagulants (NOACs) were recommended in preference to oral vitamin K antagonists (VKAs) in the 2020 updated guidelines for stroke prevention in atrial fibrillation (AF), from the European Society of Cardiology (ESC). Rivaroxaban is a NOAC that is approved in many countries worldwide for reducing the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). Purpose To explore the baseline characteristics, dosing and 2-year outcomes of patients with AF treated with rivaroxaban. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international, multicenter registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Results A total of 5043 patients were enrolled into RIVER between January 2015 and June 2017. Mean (SD) age at diagnosis was 69.5 (11.0) years and 55.7% were males. Caucasian patients represented the largest proportion of patients in RIVER (80.3%), followed by Asians (5.5%) and hispanic/latino (3.7%). Almost all patients (98.5%) were prescribed a single daily dose of rivaroxaban, most commonly 20 mg (77.3%) and 15 mg (20.4%), while a 10 mg dose was prescribed in only 2.3% of patients. During the 2-year follow-up, the rates (95% CI) of all-cause mortality, stroke/SE, and major bleeding were 2.75 (2.43 to 3.12), 0.89 (0.72; 1.11), and 1.26 (1.05 to 1.52) per 100 person years, respectively (Figure 1). The most common cardiovascular cause of death was congestive heart failure (30.4%) and myocardial infarction (11.4%). Leading non-cardiovascular causes of death were malignancy (27.4%), respiratory failure (18.9%) and infections/sepsis (13.2%). Over 2 years, 710 (14.1%) of patients discontinued rivaroxaban. The corresponding proportions at 6 months and 1 year were 7.8% and 10.8%, respectively. Out of all the patients who discontinued, 62 (8.7%) restarted rivaroxaban during their follow-up (Table 1). Conclusion During 2 years of follow up in the international, prospective RIVER registry, rivaroxaban treatment for AF was associated with low rates of stroke or major bleeding. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit

Background and objectivePatients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40–49%, HF-mrEF) left ventricular ejection fraction. MethodsAn analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. ResultsA total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03–1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03–1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. ConclusionsThis study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

Post-mortem cardiac magnetic resonance parameters in normal and diseased conditions.

Post-mortem cardiac magnetic resonance (CMR) is a non-invasive alternative to conventional autopsy. At present, diagnostic guidelines for cardiovascular conditions such as hypertrophic cardiomyopathy have not been established. We correlated post-mortem CMR images to definite conventional autopsy findings and hypothesed that elevated T2-weighted signal intensity and RV to LV area ratios can identify myocardial infarction and pulmonary emboli respectively. For this unblinded pilot sub-study, we selected cases from the original blinded study that compared post-mortem imaging to conventional autopsy in patients referred for coronial investigation between October 2014 to November 2016. Three groups of scans were selected based on the cause of death identified by conventional autopsy: non-cardiovascular causes of death with no structural cardiac abnormality i.e., control cases, acute/subacute myocardial infarction and pulmonary emboli. Left ventricular (LV) wall thickness, LV myocardial signal intensity and ventricular cavity areas were measured. Fifty-six scans were selected [39 (69.6%) males]: 37 (66.1%) controls, eight (14.3%) acute/subacute myocardial infarction and eleven (19.6%) pulmonary emboli. The median age was 61 years [Interquartile range (IQR) 50-73] and the median time from death to imaging and autopsy was 2 days (IQR 2-3) and 3 days (IQR 3-4). The septal and lateral walls were thicker {15 mm [13-17] and 15 mm [14-18]} on post-mortem CMR than published ante-mortem measurements. Areas of acute/subacute myocardial infarction had significantly higher T2-weighted signal intensity (normalised to skeletal muscle) compared to normal myocardium in those who died from other causes {2.5 [2.3-3.0.] vs. 1.9 [1.8-2.3]; P<0.001}. In cases with pulmonary emboli, there was definite RV enlargement with a larger indexed RV to LV area ratio compared to those who died from other causes {2.9 [2.5-3.0] vs. 1.8 [1.5-2.0]; P<0.001}. We present potential post-mortem CMR parameters to identify important cardiovascular abnormalities that may be beneficial when conventional autopsy cannot be performed. In patients without cardiovascular disease, LV wall thickness was found to be unreliable in diagnosing hypertrophic cardiomyopathy without histological and/or genetic testing. Elevated T2 signal intensity and RV to LV area ratios may be useful markers for acute/subacute myocardial infarction and pulmonary emboli. Larger studies will be necessary to define cut-offs.

Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial

Aims Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death.Methods and results DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo.Conclusion In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.

Recent mortality in Britain: a review of trends and explanations.

The annual percentage improvement in standardised mortality rates in the period 2011-19 was the lowest for 70years, whereas the 2001-10 value was the highest since records began in 1841. A similar slowdown occurred from around 2011 in most European Union countries, although this was generally less severe than in Britain. Life expectancy at birth actually fell in USA for three successive years in period 2014-17. The downturn in Britain since 2011 was wide-ranging, affecting young and old, women and men and the more and the less advantaged to a broadly similar extent. Year-to-year variation in mortality increased mainly due to increased volatility in winter excess mortality from 2011, but all seasons showed lower rates of improvement in underlying longer-term trends. Mortality had started to improve at the end of the decade and the 2019 value was the lowest-ever value in Britain. Two main explanations for these trends have been advanced: UK Government post-2008 austerity policies, especially in the health and social care sectors, and the role of seasonal influenza. However, the evidence for a dominant role for either of these is weak. Longer-term overall trends have been determined principally by trends in cardiovascular rather than non-cardiovascular causes of death, although recent changes in discovery and coding of dementias makes it difficult to draw firm conclusions. Healthy life expectancy trends are also affected by changes in data and methods, but the proportion of life spent in good health for both women and men over age 65 has increased slightly since 2010.

Perfil clínico y causas de muerte de los pacientes con insuficiencia cardíaca atendidos en una unidad especializada de Cardiología según su fracción de eyección

Background and objectivePatients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40–49%, HF-mrEF) left ventricular ejection fraction. MethodsAn analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. ResultsA total of 1,404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p=0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03–1.78; p=0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. ConclusionsThis study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

Cause of Death Among Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Peripheral artery disease is common and associated with high mortality. There are limited data detailing causes of death among patients with peripheral artery disease. EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) was a randomized clinical trial that assigned patients with peripheral artery disease to clopidogrel or ticagrelor. We describe the causes of death in EUCLID using mortality end points adjudicated through a clinical events classification process. The association between baseline factors and cardiovascular death was evaluated by Cox proportional hazards modeling. The competing risk of noncardiovascular death was assessed by the cumulative incidence function for cardiovascular death and the Fine and Gray method to ascertain the association between baseline characteristics and cardiovascular mortality. A total of 1263 out of 13 885 (9.1%) patients died (median follow-up: 30 months). There were 706 patients (55.9%) with a cardiovascular cause of death and 522 (41.3%) with a noncardiovascular cause of death. The most common cause of cardiovascular death was sudden cardiac death (20.1%); while myocardial infarction (5.2%) and ischemic stroke (3.2%) were uncommon. The most common causes of noncardiovascular death were malignancies (17.9%) and infections (11.9%). The factor most associated with a higher risk of cardiovascular death was age per 5 year increase (HR, 1.26 [95% CI, 1.20-1.32]). Female sex was associated with a lower risk of cardiovascular death (HR, 0.68 [95% CI, 0.56-0.82]). To evaluate the effect of noncardiovascular death as a competing risk, we superimposed the cumulative incidence function curve with the Kaplan-Meier curve. These curves closely approximated each other. After accounting for the competing risk of noncardiovascular death, the magnitude and direction of the factors associated with cardiovascular death were minimally changed. Among patients with symptomatic peripheral artery disease, noncardiovascular causes of death reflected a high proportion (40%) of deaths. Accounting for noncardiovascular deaths as a competing risk, there was not a significant change in the risk estimation for cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.

Outcomes of patients with active cancer undergoing transcatheter aortic-valve replacement

Cardiovascular diseases and cancer are the two leading causes of mortality in the world and their association is a therapeutic challenge. Current data showed that patients with active cancer and severe aortic stenosis have better survival after aortic-valve replacement in comparison with those have medical treatment. Presence of active cancer is frequently a reason to decline surgery due to the fear of periprocedural complications in this frail population and transcatheter aortic-valve replacement (TAVR) appears like the treatment of choice in this situation. However, data concerning outcomes in this case are limited and contradictory. This study aims to constitute the first French cohort of patients with active cancer undergoing TAVR in order to determine their prevalence, characteristics, perioperative outcomes and mortality. We prospectively included all consecutive patients who underwent TAVR in our institution (Nouvel Hôpital Civil, Strasbourg, France). Active cancer status at the time of the procedure was determined by a specialist physician with an anatomopathological diagnosis in all cases where it was possible. Primary endpoint was all-cause mortality during follow-up. Among 585 patients who underwent TAVR, 62 had an active cancer. All-cause mortality was significantly higher in patients with active cancer in comparison with those without cancer (38.7% vs. 20.1% respectively; P = 0.001). This excess of mortality is mainly driven by non-cardiovascular causes of death. Other periprocedural complications (major adverse cardiovascular events, bleeding, rehospitalization for heart failure, acute kidney injury) did not differ between the two groups ( Fig. 1 ). In patients who underwent TAVR, active cancer is a non-negligible comorbidity. All-cause mortality is higher in this population, mainly driven by non-cardiovascular mortality. However, periprocedural complications are not increased in this specific population.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BackgroundEpidemiologic knowledge regarding noncardiovascular and all‐cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence‐based healthcare guidelines.ObjectivesTo characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all‐cause mortality in AH and pHCM cats.AnimalsA total of 1730 client‐owned cats (722 AH, 1008 pHCM) from 21 countries.MethodsRetrospective, multicenter, longitudinal, cohort study. Long‐term health data were extracted by medical record review and owner/referring veterinarian interviews.ResultsNoncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight‐loss‐vomiting‐diarrhea‐anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All‐cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all‐cause survival was significantly shorter in pHCM (P = .0001).Conclusions and Clinical ImportanceAll‐cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

P4150Causes of death in a heart failure clinic in Spain along 17 years

Abstract Background Advances in heart failure (HF) treatment have achieved a reduction of death in HF patients in the last two decades. Indeed, not only mortality has been reduced but also the mode of death might have been modified through these years. Purpose To assess the causes of death in outpatients attended in a HF Unit since the year 2002 up to the year 2018. Methods Causes of death were classified as follows: progression of HF (worsening HF or treatment-resistant HF, in the absence of another cause); sudden death (any unexpected death, witnessed or not, of a previously stable patient with no evidence of worsening HF or any other known cause of death); acute myocardial infarction; stroke; procedural (post-diagnostic or post-therapeutic); other cardiovascular causes (e.g., rupture of an aneurysm, peripheral ischemia, or aortic dissection), and non-cardiovascular. Patients who died of unknown cause were excluded from the analysis. Fatal events were identified from the clinical records of patients with HF, hospital wards, the emergency room, general practitioners, or by contacting the patient's relatives. Furthermore, data were verified from the databases of the Catalan and Spanish Health Systems. Trends on every cause of death were assessed by linear regression. Results Since August 2001 to May 2018, 2295 HF patients were admitted to the HF clinic (age 66.4±12.8 years, 71% men, 49% from ischemic aetiology, mean LVEF 35.2% ± 14). During the 17 years of the study, 1201 deaths were recorded. Seventy-eight patients (6.5% of deaths) were excluded due to unknown cause of death. The evolution in the mode of death by years is shown in the figure. Two trends were observed: a decrease in sudden death (p=0.05) and a very significant linear increase in non-cardiovascular causes of death (p&lt;0.001). The decrease of sudden death was mainly driven from changes observed in the first 10 years (p=0.014); thereafter the incidence of sudden death remained stable (p=0.18). Remarkably we did not observe significant changes in HF progression as mode of death (p=0.17). Conclusions During the 17 years of the study, a very significant trend towards higher percentage of non-cardiovascular deaths was progressively observed. On the other hand, percentage of sudden death showed a gradual decrease, mainly driven from the changes observed in the first 10 years.

P1543Causes of death in patients with myocardial infarction, and non-ischemic myocardial injury

Abstract Background Information about causes of death in patients with non-ischemic acute and chronic myocardial injury is limited. Purpose To explore causes of death, mortality rates and risks of cardiovascular and non-cardiovascular causes of death in patients with type 1 MI (T1MI), type 2 MI (T2MI), and acute and chronic myocardial injury compared with patients without myocardial injury. Methods From a cohort of 39,558 patients who visited the ED at our University Hospital during 2011–2014 and who had high-sensitivity cardiac troponin T (hs-cTnT) levels measured, we identified 3,853 patients with hs-cTnT levels above the 99th percentile value and categorised them into the following groups: i) T1MI, ii) T2MI, iii) acute and iv) chronic myocardial injury. Among these we included all patients who died during follow-up. Causes of death were obtained from the Swedish Cause-of-Death register. All deaths among patients without myocardial injury (n=819) from the same cohort were used for comparison. We calculated incidence rates of cause-specific deaths in the different groups and used logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age and sex for different causes of death, using patients without myocardial injury as referent. Results 2,285 patients died during follow-up at a mean age of 76 (±13) years of whom 46% were female. Patients without myocardial injury died at a younger age (mean 70 years) compared with patients in the groups with myocardial injury (mean 79–82 years). The proportion of cardiovascular (CV) deaths were considerably higher in patients with T1MI (48%), T2MI (39%), acute (43%), and chronic (45%) myocardial injury compared with patients with no myocardial injury (25%). 42% of patients without myocardial injury died from cancer, compared with 18% to 24% among patients with different myocardial injury. Age- and sex-adjusted incidence rates for CV-death were similar for T1MI, T2MI and acute myocardial injury (27 per 100 person-years), slightly lower in patients with chronic myocardial injury (22 per 100 person-years) and almost half in patients with no myocardial injury (14 per 100 person-years). The adjusted ORs with 95% CIs for CV death were highest in patients with T1MI (1.99, 1.48–2.69) and acute myocardial injury (1.72, 1.29–2.11), while only marginally lower in patients with T2MI and chronic myocardial injury (1.43, (0.94–2.16), and 1.65, (1.29–2.11) respectively). Conclusions Patients with T1MI and acute or chronic myocardial injury have similar risks to die from cardiovascular causes. Patients without myocardial injury died younger and the proportions of cancer-related deaths were twice as high as in the groups with myocardial injury. Proportions and risks of CV-death among patients with T2MI were higher than in patients without myocardial injury, but lower than in patients with T1MI and acute or chronic myocardial injury. Acknowledgement/Funding None

6129Temporal trends and patterns in cause-specific mortality and hospitalisations after incident heart failure: a longitudinal analysis of 86,000 individuals

Abstract Background The past two decades have brought considerable improvements in heart failure care. Clinical trials have demonstrated effectiveness of several different treatments in reducing mortality and hospitalisations, and observational studies have shown that these treatments are increasingly being used in many countries. Little is known about whether these changes have been reflected in patient outcomes in routine clinical settings. Methods We used anonymised electronic health records that link information from primary care, secondary care, and the national death registry to investigate 86,000 individuals with newly diagnosed heart failure between 2002 and 2013 in the UK. We computed all-cause and cause-specific mortality rates and number of hospitalisations in the first year following diagnosis. We used Poisson regression models to calculate category-specific rate ratios and 95% confidence intervals, adjusting for patients' age, sex, region, socioeconomic status and 17 major comorbidities. Findings One year after initial heart failure diagnosis, all-cause mortality rates were high (32%) and did not change significantly over the period of study (adjusted rate ratio (RR) 2013 vs 2002: 0.94 [0.88, 1]). Overall rates masked diverging trends in cause-specific outcomes: a decline in cardiovascular mortality (RR: 0.74 [0.68, 0.81]) was offset by an increase in non-cardiovascular mortality (RR: 1.28 [1.17, 1.39]), largely due to infections and chronic respiratory conditions. Sub-group analyses further showed that overall mortality declined among patients under 80 years of age (RR 2013 vs 2002: 0.79 [0.71, 0.88]), although not in older age groups (RR 2013 vs 2002: 0.97 [0.9, 1.06]). After cardiovascular causes (43%), the major causes of death identified in 2013 were neoplasms (15%), respiratory conditions (12%), and infections (11%). Hospital admissions within a year of heart failure diagnosis were common (1.15 hospitalisations per patient-year at risk), changed little over time (RR: 0.96 [0.92, 0.99]), and were largely (60%) due to non-cardiovascular causes. Interpretation Despite increased use of life-saving interventions, overall mortality and hospitalisations following a new diagnosis of heart failure have changed little over the past decade. Improved prognosis among young and middle-aged patients marks an important achievement and attests of complex barriers to progress in elderly patients. The shift from cardiovascular to non-cardiovascular causes of death suggest that management of associated comorbidities might offer additional opportunities to improve patients' prognosis. Acknowledgement/Funding British Heart Foundation, National Institute for Health Research, UK Research and Innovation.

Prophylactic implantable cardioverter-defibrillator in the very elderly.

Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with <80 years old controls matched for sex and underlying heart disease (ischaemic and dilated cardiomyopathy). A total of 300 ICD recipients were enrolled in this specific analysis, including 150 patients ≥80 years (mean age 81.9 ± 2.0 years; 86.7% males) and 150 controls (mean age 61.8 ± 10.8 years). Among older patients, 92 (75.6%) had no more than one associated comorbidity. Most subjects in the elderly group got an ICD as part of a cardiac resynchronization therapy procedure (74% vs. 46%, P < 0.0001). After a mean follow-up of 3.0 ± 2 years, 53 patients (35%) in the elderly group died, including 38.2% from non cardiovascular causes of death. Similar proportion of patients received ≥1 appropriate therapy (19.4% vs. 21.6%; P = 0.65) in the elderly group and controls, respectively. There was a trend towards more early perioperative events (P = 0.10) in the elderly, with no significant increase in late complications (P = 0.73). Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

Coronary Artery Calcification and Mortality Risk in Patients With Severe Mental Illness.

Background Cardiovascular mortality is the leading contributor to the shortened life expectancy in patients with severe mental illness (SMI), but efforts to predict cardiovascular outcomes in these patients have been lacking. In this study, we aimed to determine the severity of coronary artery calcification (CAC), and its effect on mortality rates in patients with SMI, compared with the general population. Methods All individuals with a registered cardiac computed tomography for calcium scoring in the Western Denmark Heart Registry, from January 1, 2008 to December 31, 2016, were included. We identified patients diagnosed with SMI ( International Classification of Diseases, Tenth Revision: F20, F30, F31), whereas the remaining individuals were used as a comparison group. Results Among 48 757 individuals, including 564 patients with SMI (1.2%), we found no difference in CAC score between patients with SMI and the comparison group. SMI patients with CAC >100 had an increased mortality rate (hazard ratio, 3.16; 95% CI, 1.41-7.06), as well as SMI patients with CAC <100 (hazard ratio, 3.95; 95% CI, 2.36-6.62), compared with the comparison group with CAC <100 as reference, adjusted for age, sex, and calendar period. Conclusions Patients with SMI have increased cardiovascular risks, but show no difference in CAC score, compared with the comparison group. Mortality rates were increased in patients with SMI, independent of CAC severity; however, the relatively large number of noncardiovascular causes of death in this sample might indicate other contributing factors to death than coronary artery disease in this sample of SMI patients.

Outcome of patients ≥ 60 years of age after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

IntroductionThe outcome of patients ≥ 60 years of age after alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) remains unresolved. We sought to determine the long-term survival and the causes of death in this population.Material and methodsWe enrolled 156 consecutive patients (69 ±6 years, 69% women, follow-up: 4.8 ±3.5 years) who underwent ASA at ≥ 60 years of age.ResultsThe 30-day mortality rate was 1.3%. At the last check-up, 81% of patients were in New York Heart Association class ≤ 2 and 76% had a left ventricular outflow tract gradient (LVOG) ≤ 30 mm Hg. A total of 39 patients died (51% of cardiovascular causes, 44% of non-cardiovascular causes, 5% of unknown causes) during the 734 patient-years. The annual sudden mortality, the sudden mortality and the all-cause mortality rates were 0.5%, 1.1%, and 4.8%, respectively. The all-cause mortality was higher compared to the age- and sex-matched general population (p = 0.002).ConclusionsAlcohol septal ablation was safe and effective in the long-term follow-up. We observed a reduced life expectancy compared to the age- and sex-matched general population. Mortality was almost equally due to cardiovascular and non-cardiovascular causes of death.

Contemporary Management of Heart Failure in the Elderly.

The foundation of the treatment of heart failure with reduced ejection fraction is a number of pharmacotherapies shown to reduce morbidity and mortality in large randomised multinational clinical trials. These include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, and more recently, a combined angiotensin receptor blocker neprilysin inhibitor, sacubitril/valsartan. In select cases, digoxin, ivabradine and hydralazine with isosorbide dinitrate have a role to play in the treatment of heart failure with reduced ejection fraction. On this foundation, other more advanced treatments such as implantable cardioverter defibrillators and cardiac resynchronisation therapy are recommended in guidelines for the treatment of heart failure with reduced ejection fraction (i.e. an ejection fraction of ≤ 40%) and for a select few there remains the option of mechanical circulatory support and cardiac transplantation. The efficacy of pharmacotherapy does not vary by age and each of these therapies should be considered in all patients, irrespective of age. Other factors such as co-morbidities like renal dysfunction may limit the use of some of these drugs in the elderly. Decision making with regard to device therapy is more complex; the likelihood of competing non-cardiovascular causes of death and life expectancy need to be considered. Despite multiple treatment options for heart failure with reduced ejection fraction, the options for heart failure with preserved ejection fraction are limited. In the absence of robust outcomes data from a large randomised trial, a mineralocorticoid receptor antagonist is a reasonable therapy to reduce the risk of hospitalisation for heart failure in patients with heart failure with preserved ejection fraction.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study.

It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group. We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]. No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.

Secular Trends in Infection-Related Mortality after Kidney Transplantation.

Infections are the most common noncardiovascular causes of death after kidney transplantation. We analyzed the current infection-related mortality among kidney transplant recipients in a nationwide cohort in Finland. Altogether, 3249 adult recipients of a first kidney transplant from 1990 to 2012 were included. Infectious causes of death were analyzed, and the mortality rates for infections were compared between two eras (1990-1999 and 2000-2012). Risk factors for infectious deaths were analyzed with Cox regression and competing risk analyses. Altogether, 953 patients (29%) died during the follow-up, with 204 infection-related deaths. Mortality rate (per 1000 patient-years) due to infections was lower in the more recent cohort (4.6; 95% confidence interval, 3.5 to 6.1) compared with the older cohort (9.1; 95% confidence interval, 7.6 to 10.7); the incidence rate ratio of infectious mortality was 0.51 (95% confidence interval, 0.30 to 0.68). The main causes of infectious deaths were common bacterial infections: septicemia in 38% and pulmonary infections in 45%. Viral and fungal infections caused only 2% and 3% of infectious deaths, respectively (such as individual patients with Cytomegalovirus pneumonia, Herpes simplex virus meningoencephalitis, Varicella zoster virus encephalitis, and Pneumocystis jirovecii infection). Similarly, opportunistic bacterial infections rarely caused death; only one death was caused by Listeria monocytogenes, and two were caused by Mycobacterium tuberculosis. Only 23 (11%) of infection-related deaths occurred during the first post-transplant year. Older recipient age, higher plasma creatinine concentration at the end of the first post-transplant year, diabetes as a cause of ESKD, longer pretransplant dialysis duration, acute rejection, low albumin level, and earlier era of transplantation were associated with increased risk of infectious death in multivariable analysis. The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.

Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury

BackgroundData outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. MethodsDuring a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. ResultsOverall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P < .0001). In patients with type 1 myocardial infarction, 61.3% died from cardiovascular causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P < .0001). The overall mortality and the causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. ConclusionsPatients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate.