The Benefit of Percutaneous Coronary Intervention Before Transcatheter Aortic Valve Replacement: A Multicenter Retrospective Outcome-Based Study.

There is inadequate evidence regarding the role of percutaneous coronary intervention (PCI) in patients who underwent transcatheter aortic valve replacement (TAVR). The current American Heart Association/American College of Cardiology guidelines are limited to class 2A recommendations for pre-TAVR revascularization in the setting of hemodynamically significant left main (LM), proximal left anterior descending (pLAD), or extensive bifurcation disease regardless of angina status. We performed a multicenter, retrospective, observational study assessing the benefit of PCI in patients with coronary artery disease who underwent transfemoral TAVR for severe symptomatic aortic stenosis. Patients were divided into 2 cohorts: (1) patients who did not undergo pre-TAVR PCI within the preceding 12 months (no-PCI group) and (2) patients who received pre-TAVR PCI within the preceding 12 months (PCI group). The primary outcome was defined as the composite end point of in-hospital and 30-day adverse events, including all-cause mortality, cardiac arrest, and myocardial infarction. Subgroup analyses were performed on patients with LM and/or pLAD disease and other high-risk features, including angina and heart failure. Comparisons were made between 1,809 consecutive patients (1,364 in the no-PCI group and 445 in the PCI group). There were no differences between the 2 cohorts regarding the primary composite outcome (2.0% vs 2.8%, p = 0.918) or individual secondary outcomes. Although LM/pLAD disease, New York Heart Association classes III to IV, and Society of Thoracic Surgeons risk score ≥8 were all independent predictors of the primary outcome, none of the subgroups demonstrated a benefit favoring PCI. In conclusion, there is no observed benefit from PCI within 12 months pre-TAVR in patients with severe aortic stenosis and concomitant coronary artery disease, including patients with LM/pLAD disease.

Sex and age-specific interactions of coronary atherosclerotic plaque onset and prognosis from coronary computed tomography.

AIMS: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. METHODS AND RESULTS: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). CONCLUSION: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease with high morbidity and mortality. OBJECTIVES: To describe temporal trends in IE incidence, mortality and survival over the last 30 years. METHODS: Nineteen high-income countries (the 'EU 15+') were included. Age-standardised and sex-stratified incidence rates (ASIRs) and mortality rates (ASMRs) for IE were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019, and mortality to incidence ratios (ASMIRs) were calculated. Trends were analysed using Joinpoint regression analysis. RESULTS: ASIRs were higher in males than females and increased in both sexes in all countries between 1990 and 2019. A recent steep rise in ASIRs was noted in several countries including the UK, the USA and Germany. ASMRs increased for both sexes in all countries except Finland and Austria. The largest increase in ASMR was observed in females in Italy (+246%). ASMIRs were generally higher in females compared to males, with large increases in ASMIRs (indicating worsening survival) at the end of the 20th century, but more recent stabilisation or decline across the study cohort. CONCLUSIONS: While the incidence and mortality of IE have increased over the last 30 years, recent data suggest that these trends have plateaued or reversed in most countries studied. However, a recent surge in incidence in several countries (including the USA and UK) is of concern, while unfavourable outcomes in females also merit attention. More encouragingly, this analysis provides the first indication of improving IE survival at population level, supporting recent advances in diagnosis and treatment.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Acute mitral regurgitation and cardiogenic shock: Reverse takotsubo cardiomyopathy or acute coronary syndrome?

Reverse takotsubo cardiomyopathy (rTCM) is characterized by basal ballooning and accounts for approximately 1% of all TCM. To our knowledge, there have been no reports describing rTCM complicated by acute, severe, transient mitral regurgitation (MR). A 75-year-old woman with a medical history of hypertension, dyslipidemia, and anxiety presented to the hospital with 2 days of substernal chest pain, dyspnea, and nausea. Initial troponin was 0.203 ng/mL, and electrocardiography showed sinus tachycardia at 121 bpm, with inferior and anterolateral ST segment depressions. Transthoracic echocardiogram (TTE) found an ejection fraction of 30%, apical hyperkinesis, severe hypokinesis of the basal to mid segments of the left ventricle (LV), and a severe central MR jet. Cardiac angiography demonstrated non-obstructive coronary artery disease, and elevated left ventricular end diastolic pressures. Left ventriculography showed a hyperdynamic apex and severe basal hypokinesis. The patient was treated medically, clinical status improved, and was discharged on day 3. TTE four weeks later, showed an ejection fraction of 60-65%, mild MR, and normal LV function. rTCM is the rarest variant of TCM. Basal and mid-myocardial stunning can cause severe secondary MR leading to acute congestive heart failure, mimicking acute coronary syndrome with acute MR. rTCM with rapidly reversible severe MR has not previously been described. .

Incidence and Mortality Trends of Atrial Fibrillation/Atrial Flutter in the United States 1990 to 2017.

Atrial fibrillation (AF) and flutter (AFL) are the most common clinically significant arrhythmias in older adults with an increasing disease burden due to an aging population. However, up-to-date trends in disease burden and regional variation remain unknown. In an observational study utilizing the Global Burden of Disease (GBD) database, age-standardized mortality and incidence rates for AF overall and for each state in the United States (US) from 1990 to 2017 were determined. All analyses were stratified by gender. The relative change in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) over the observation period were determined. Trends were analyzed using Joinpoint regression analysis. The mean ASIR per 100,000 population for men was 92 (+/-8) and for women was 62 (+/-5) in the US in 2017. The mean ASDR per 100,000 population for men was 5.8 (+/-0.3) and for women was 4.4 (+/-0.4). There were progressive increases in ASIR and ASDR in all but 1 state. The states with the greatest percentage change in incidence were New Hampshire (+13.5%) and Idaho (+16.0%) for men and women, respectively. The greatest change regarding mortality was seen in Mississippi (+26.3%) for men and Oregon (+53.8%) for women. In conclusion these findings provide updated evidence of increasing AF and/or AFL incidence and mortality on a national and regional level in the US, with women experiencing greater increases in incidence and mortality rates. This study demonstrates that the public health burden related to AF in the United States is progressively worsening but disproportionately across states and among women.

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PURPOSE: To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. MATERIALS AND METHODS: Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. RESULTS: At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). CONCLUSION: When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease.

BACKGROUND: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. METHODS: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. RESULTS: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality (P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality (P < .0001) and death or MI (P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. CONCLUSIONS: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD.

Coronary computed tomographic angiography as a gatekeeper to invasive diagnostic and surgical procedures: results from the multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter) registry.

OBJECTIVES: This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA). BACKGROUND: CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-CCTA patterns of follow-up ICA and REV are incompletely defined. METHODS: We examined 15,207 intermediate likelihood patients from 8 sites in 6 countries; these patients were without known CAD, underwent CCTA, and were followed up for 2.3 ± 1.2 years for all-cause mortality. Coronary artery stenosis was judged as obstructive when ≥50% stenosis was present. A multivariable logistic regression was used to estimate ICA use. A Cox proportional hazards model was used to estimate all-cause mortality. RESULTS: During follow-up, ICA rates for patients with no CAD to mild CAD according to CCTA were low (2.5% and 8.3%), with similarly low rates of REV (0.3% and 2.5%). Most ICA procedures (79%) occurred ≤3 months of CCTA. Obstructive CAD was associated with higher rates of ICA and REV for 1-vessel (44.3% and 28.0%), 2-vessel (53.3% and 43.6%), and 3-vessel (69.4% and 66.8%) CAD, respectively. For patients with <50% stenosis, early ICA rates were elevated; over the entirety of follow-up, predictors of ICA were mild left main, mild proximal CAD, respectively, or higher coronary calcium scores. In patients with <50% stenosis, the relative hazard for death was 2.2 (p = 0.011) for ICA versus no ICA. Conversely, for patients with CAD, the relative hazard for death was 0.61 for ICA versus no ICA (p = 0.047). CONCLUSIONS: These findings support the concept that CCTA may be used effectively as a gatekeeper to ICA.

Mortality risk in symptomatic patients with nonobstructive coronary artery disease: a prospective 2-center study of 2,583 patients undergoing 64-detector row coronary computed tomographic angiography.

OBJECTIVES: We examined mortality risk in relation to extent and composition of nonobstructive plaques by 64-detector row coronary computed tomographic angiography (CCTA). BACKGROUND: The prognostic significance of nonobstructive coronary artery plaques by CCTA is poorly understood. METHODS: We prospectively evaluated consecutive adults from 2 centers undergoing 64-detector row CCTA without prior documented coronary artery disease (CAD) and without obstructive (≥50%) CAD by CCTA. Luminal diameter stenosis severity was classified for each segment as none (0%) or mild (1% to 49%), and plaque composition was classified as noncalcified, calcified, or mixed. RESULTS: During 3.1 ± 0.5 years, 54 intermediate-term (≥90 days) deaths occurred among 2,583 patients (2.09%), with 4 early (<90 days) deaths. Adjusted for CAD risk factors, the presence of any nonobstructive plaque was associated with higher mortality (hazard ratio [HR]: 1.98, 95% confidence Interval [CI]: 1.06 to 3.69, p = 0.03), with the highest risk among those exhibiting nonobstructive CAD in 3 epicardial vessels (HR: 4.75, 95% CI: 2.10 to 10.75, p = 0.0002) or ≥5 segments (HR: 5.12, 95% CI: 2.16 to 12.10, p = 0.0002). Higher mortality for nonobstructive CAD was observed even among patients with low 10-year Framingham risk (3.4%, p < 0.0001) as well as those with no traditional, medically treatable CAD risk factors, including diabetes mellitus, hypertension, and dyslipidemia (6.7%, p < 0.0001). No independent relationship between plaque composition and incident mortality was observed. Importantly, patients without evident plaque experienced a low rate of incident death during follow-up (0.34%/year). CONCLUSIONS: The presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment.