The obesity paradox in the stress echo lab: fat is better for hearts with ischemia or coronary microvascular dysfunction.

BACKGROUND: Obesity is an independent risk factor for coronary artery disease (CAD), but once CAD has developed it has been associated with improved survival ("obesity paradox"). AIM: To assess how obesity affects prognosis in patients with or without inducible ischemic regional wall motion abnormalities (RWMA) and/or abnormal coronary flow velocity reserve (CFVR) during stress echocardiography (SE). METHODS: In an observational retrospective two- center study design, we analyzed 3249 consecutive patients (1907 men; age 66 ± 12 years; body mass index, BMI, 26.9 ± 4.1 kg/m2) with known (n = 1306) or suspected (n = 1943) CAD who underwent dipyridamole SE with simultaneous evaluation of RWMA and CFVR. All-cause death was the outcome end-point. RESULTS: 1075 patients were lean (BMI 18.5-24.9 kg/m2), 1523 overweight (BMI 25.0-29.9 kg/m2), and 651 obese (≥30.0 kg/m2). Ischemic test result for RWMA occurred in 28 (3%) lean, 69 (4%) overweight, and 28 (4%) obese patients (p = 0.03). An abnormal CFVR (≤2.0) was found in 281 (26%) lean, 402 (26%) overweight and 170 (26%) obese patients (p = 0.99). During 68 ± 44 months of follow-up, 496 (15%) patients died. At multivariable Cox analysis, BMI ≥ 30 was an independent predictor of reduced mortality in the 878 patients with stress-induced (≥2 segments) RWMA and/or CFVR abnormality (HR 0.58, 95% CI 0.40-0.84; p = 0.003), while showed no effect at univariate analysis in the 2371 patients with no RWMA and normal CFVR (HR 1.04, 95% CI 0.74-1.46; p = 0.84). CONCLUSIONS: Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA.

Clinical, hemodynamic, and functional variables affecting success rate of coronary flow velocity reserve detection during vasodilator stress echocardiography.

AIM: Stress echocardiography (SE) with state-of-the-art imaging protocol allows a comprehensive assessment of regional wall-motion abnormalities and Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD). We sought to assess the variables potentially impacting on success rate of SE with CFVR. METHODS AND RESULTS: In a single-center, prospective, observational study design, from 2007 to 2019, we enrolled 2989 consecutive patients (age 67 ± 12 years; 1723 men) referred for SE, without contrast, for chronic known (n = 1130) or suspected (n = 1859) coronary syndromes. Coronary flow velocity reserve was measured as stress/rest peak diastolic flow velocity. The same operator (LC) performed all examinations with the same machine (GE Vivid 7). Interpretable CFVR was obtained in 2808 patients (feasibility = 93.9%). Overall success rate was lowest (91.4%) in 2007-2008 and steadily rose to 97.8% in 2017-2019 (P for trend <.0001). Feasibility was excellent for men (93.7%) and women (94.3%) (P = .47) across all values of body mass index (BMI): <25 (P = .09), 25-29 (P = .84), and ≥30 (P = .23). At multivariable logistic regression analysis, women with BMI ≥ 30 (OR 1.94, 95% CI 1.14-3.29, P = .02), resting heart rate ≥77 beats/min (OR 2.25, 95% CI 1.64-3.11; P < .0001), and stress-induced ischemia in the LAD territory (OR 3.14, 95% CI 1.67-5.90; P < .0001) predicted unfeasible CFVR. CONCLUSION: Vasodilator SE with CFVR combined with wall-motion analysis is highly feasible also without contrast although with a slight decline in presence of high resting heart rate (reducing diastolic time essential for flow imaging), women with BMI ≥ 30 (increasing tissue thickness interposed between transducer and artery), and anterior ischemia (for underlying low-absent anterograde flow for severely stenotic or occluded LAD).

ANMCO Position Paper: hospital discharge planning: recommendations and standards.

The hospital discharge is often poorly standardized and affected by discontinuity and fragmentation of care, putting patients at high risk of both post-discharge adverse events and early readmission. The present ANMCO document reviews the modifiable components of the hospital discharge process related to adverse events or re-hospitalizations and suggests the optimal methods for redesigning the whole discharge process. The key principles for proper hospital discharge or transfer of care acknowledge that the hospital discharge: • is not an isolated event, but a process that has to be planned as soon as possible after the admission, ensuring that the patient and the caregiver understand and contribute to the planned decisions, as equal partners; • is facilitated by a comprehensive systemic approach that begins with a multidimensional evaluation process; • must be organized by an operator who is responsible for the coordination of all phases of the hospital patient journey, involving afterward the general practitioner and transferring to them the information and responsibility at discharge; • is the result of an integrated multidisciplinary team approach; • appropriately uses the transitional and intermediate care services; • is carried out in an organized system of care and continuum of services; and • programs the passage of information to after-discharge services.

A multidisciplinary consensus document on follow-up strategies for patients treated with percutaneous coronary intervention.

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document.

Influence of depression and anxiety on circulating endothelial progenitor cells in patients with acute coronary syndromes.

OBJECTIVES: Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). METHODS: Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. RESULTS: Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. CONCLUSIONS: The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders.

Tailored use of transradial access for above-the-knee angioplasty.

PURPOSE: To report the results and complications of a single-center experience of above-the-knee angioplasty via transradial access (TRA). METHODS: In a prospective study, 110 consecutive patients (88 men; mean age 72 years, range 37-90) referred for critical limb ischemia (26, 24%) or claudication were eligible for lower limb angioplasty via TRA (patients with TASC D lesions of the superficial femoral artery and below-the-knee lesions were excluded). RESULTS: The majority of patients (84, 76%) were treated via a left TRA. A total of 170 lesions were addressed, of which 38 (22%) were occlusions; 113 stents were positioned in 82 patients. The overall technical success rate was 91%, with a 63% success rate in occlusions and a 98% success rate in stenoses; by location, the success rates were 91% in suprainguinal lesions and 90% in infrainguinal lesions. No hemorrhagic or local complications requiring surgery were observed. At 1-month follow-up, 101 patients had a downward shift of at least one category in the Rutherford classification of symptoms (clinical success rate 92%); 18 (16%) patients had occlusion of their access radial artery, but none had symptoms or discomfort. CONCLUSION: The present study demonstrates that TRA is a safe and effective approach for lower extremity arterial revascularization, at least for interventionists with longstanding experience in TRA and in selected anatomical subsets.

Prognostic implication of Doppler echocardiographic derived coronary flow reserve in patients with left bundle branch block.

AIMS: Myocardial ischaemia during pharmacological stress echocardiography is a strong prognostic predictor in patients with a left bundle branch block (LBBB). However, the additive value of Doppler-derived coronary flow reserve (CFR) during pharmacological stress testing remains to be investigated in this subset of patients. METHODS AND RESULTS: The study group consisted of 324 LBBB patients (187 men; age 68 ± 10 years) with known (n = 74) or suspected (n = 250) coronary artery disease who had undergone dipyridamole (up to 0.84 mg/kg over 6') stress echocardiography with CFR assessment of left anterior descending (LAD) by Doppler. A value of CFR ≤ 2.0 was considered abnormal. The median duration of follow-up was 15 months (first to third quartile: 8-34 months). Of the 324 patients, 52 (16%) had ischaemia at stress echo by wall motion criteria, and 139 (43%) had a CFR ≤ 2. During follow-up, 51 (16%) events occurred: 37 deaths and 14 myocardial infarctions (MIs). Age (HR: 1.09, 95% CI: 1.04-1.15, P < 0.0001), resting wall motion score index (HR: 5.29, 95% CI: 2.36-11.89, P < 0.0001), smoking habit (HR: 4.38, 95% CI: 1.93-9.91, P < 0.0001), and CFR ≤ 2 (4.69, 95% CI: 1.96-11.19, P = 0.001) were independently correlated with mortality, while CFR ≤ 2 (HR: 3.91, 95% CI: 1.90-8.04, P < 0.0001), age (HR: 1.06, 95% CI: 1.02-1.10, P = 0.001), smoking habit (HR: 2.25, 95% CI: 1.18-4.30, P = 0.01), ischaemia at stress echo (HR: 2.30, 95% CI: 1.11-4.77, P = 0.02), and resting wall motion score index (HR: 2.17, 95% CI: 1.11-4.25, P = 0.02) were independently correlated with death or MI. Four-year mortality and 4-year hard event rate were markedly higher in patients with CFR ≤ 2 than in those with CFR >2 (49 vs. 6% and 56 vs. 8%, respectively; P < 0.0001 for both). A CFR of ≤ 2 was associated with a significantly higher annual hard event rate independently of age, sex, ejection fraction, history of coronary artery disease, diabetes, and hypertension. Moreover, it was correlated with an increased (P < 0.0001) yearly mortality and event rate in patients with non-ischaemic stress echo conducted on therapy. At incremental analysis, a CFR of ≤ 2 added prognostic value to clinical findings, resting wall motion score index, ongoing anti-ischaemic therapy, and ischaemia at stress echo when both death and death or MI were the clinical endpoints. CONCLUSIONS: Abnormal CFR on LAD is a strong and independent indicator of mortality and death or MI in patients with LBBB, and is associated with markedly increased risk also in the subset of patients with stress echo negative for ischaemia on therapy.

[Cardiovascular risk profile and lifestyle habits in a cohort of Italian cardiologists. Results of the SOCRATES survey]. / Profilo di rischio cardiovascolare e stili di vita in una coorte di cardiologi Italiani. risultati della survey SOCRATES (Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists).

OBJECTIVES: To offer a snapshot of the personal health habits of Italian cardiologists, the Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists (SOCRATES) study was undertaken. BACKGROUND: Cardiologists' cardiovascular profile and lifestyle habits are poorly known worldwide. METHODS: A Web-based electronic self-reported survey, accessible through a dedicated website, was used for data entry, and data were transferred via the web to a central database. The survey was divided in 4 sections: baseline characteristics, medical illnesses and traditional cardiovascular risk factors, lifestyle habits and selected medication use. The e-mail databases of three national scientific societies were used to survey a large and representative sample of Italian cardiologists. RESULTS: During the 3-month period of the survey, 1770 out of the 5240 cardiologists contacted (33.7%) completed and returned one or more sections of the questionnaire. More than 49% of the participants had 1 out of 5 classical risk factors (e.g. hypertension, hypercholesterolemia, active smoking, diabetes and previous vascular events). More than 28% of respondents had 2 to 5 risk factors and only 22.1% had none and therefore, according to age and sex, could be considered at low-intermediate risk. Despite the reported risk factors, more than 90% of cardiologists had a self-reported risk perception quantified as mild, such as low or intermediate. Furthermore, overweight/obesity, physical inactivity and stress at work or at home were commonly reported, as well as a limited use of cardiovascular drugs, such as statins or aspirin. CONCLUSIONS: The average cardiovascular profile of Italian cardiologist is unlikely to be considered ideal or even favorable according to recent statements and guidelines regarding cardiovascular risk. Thus, there is a large room for improvement and a need for education and intervention.

Prognostic implication of stress echocardiography in 6214 hypertensive and 5328 normotensive patients.

Aims To compare the prognostic implication of stress echocardiography (SE) in a large cohort of hypertensive and normotensive patients with known or suspected coronary artery disease (CAD). The relative prognostic meaning of the SE result in hypertensive and normotensive patients remains to be addressed. Methods and results The study group was formed by 11 542 patients (6214 hypertensive patients; 5328 normotensive patients) who underwent exercise (n= 686), dobutamine (n= 2524), or dipyridamole (n= 8332) SE for evaluation of known (n= 4563) or suspected (n= 6979) CAD. Patients were followed up for a median of 25 months (1st quartile, 7; 3rd quartile, 57). Ischaemia on SE (new wall motion abnormality) was detected in 3209 (28%) patients. During follow-up, 1587 events (924 deaths, 663 non-fatal infarctions) occurred. Patients (n= 2764) undergoing revascularization were censored. The annual event rate was 7.0% in hypertensive and 5.7% in normotensive patients (P = 0.02) with known CAD, and 3.7% in hypertensive and 2.4% in normotensive patients (P< 0.0001) with suspected CAD. Ischaemia on stress echo, resting wall motion abnormality (RWMA), age, male sex, and diabetes mellitus were multivariable prognostic predictors in both patient groups. Analysing data according to the interaction of prognostically important echocardiographic covariates, such as ischaemia on SE and RWMA, an effective risk assessment was obtained in hypertensive as well as normotensive patients. The annual event rate was markedly higher in hypertensive than in normotensive patients with no ischaemia and no RWMA (2.5 and 1.7%, P = 0.0001). Finally, the incremental prognostic value of inducible ischaemia over clinical evaluation and resting left ventricular function was greater in hypertensive than in normotensive patients both with known and suspected CAD. Conclusion The SE result allows an effective prognostication in hypertensive and normotensive patients. However, a non-ischaemic test predicts better survival in normotensive than in hypertensive patients with no RWMA.

Reduced coronary flow velocity reserve and blunted heart rate reserve identify a higher risk group in patients with chest pain and negative emergency department evaluation.

To estimate the prognostic value of stress echo (SE) with the assessment of coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) in patients admitted for chest pain with non-diagnostic EKG, negative troponin, and without inducible regional wall motion abnormalities (RWMA). 658 patients (age 67 ± 12 years) admitted to our Emergency Department with chest pain, non-diagnostic EKG, and negative serial troponin underwent dipyridamole (0.84 mg/kg in 6') SE with simultaneous assessment of RWMA, CFVR in the left anterior descending artery, and HRR as peak/rest heart rate. The outcome measure was all-cause mortality. Of the 658 patients initially enrolled, 20 (3%) showed RWMA during SE and were referred to ischemia-driven revascularization. In the remaining 638, CFVR was abnormal (≤ 2.0) in 148 patients (23%). HRR was abnormal (≤ 1.22 in patients in sinus rhythm, or ≤ 1.17 in patients with permanent atrial fibrillation) in 196 patients (31%). During a follow-up of 7.3 ± 4.3 years, 151 (24%) patients died. Survival at 8 years was 93% in patients with normal CFVR and HRR, 76% in patients with abnormal CFVR only, 73% in patients with abnormal HRR only, and 38% in those with abnormal CFVR and HRR (p < 0.0001). At multivariable analysis, abnormal CFVR (HR 1.49, 95% CI 1.05-2.10, p = 0.02) and abnormal HRR (HR 2.01, 95% CI 1.43-2.84, p < 0.0001) were independent predictors of survival. In admitted patients with non-ischemic EKG, negative serial troponin, and without RWMA during dipyridamole SE, a reduced CFVR and blunted HRR independently identify a subset with worse survival in the long term. Upper panel: Color and pulsed-wave Doppler with the electrocardiographic lead tracing of Four different response patterns (from left to right): normal CFVR and HRR; normal CFVR, abnormal HRR; abnormal CFVR, normal HRR; abnormal CFVR and HRR. Lower panel: The annualized death rate for each of the four groups with negative SE for RWMA and stratified according to the presence of CFVR and HRR: none, one, or two abnormalities.

[A rare case of myocarditis and pulmonary embolism after BNT162b2 mRNA vaccine]. / Raro caso di miocardite ed embolia polmonare dopo vaccino a mRNA BNT162b2.

In the clinical research arsenal, the COVID-19 vaccines are the strongest weapons against the most important worldwide sanitary crisis of the last centuries. Even if vaccine adverse events have mild clinical relevance, several thromboembolic events occurring after adenoviral recombinant vaccine administration have been reported. Cases of myocarditis and pericarditis after administration of mRNA vaccines have also recently been described. We report the case of a patient who suffered from two rare adverse events after BNT162b2 mRNA vaccine administration (Pfizer-BioNTech): acute myocarditis and pulmonary embolism. Although the temporal consequentiality does not demonstrate a causal link, the strong analogies emerging in the latest clinical reports suggest a possible relation. Further studies are needed to understand the potential mechanisms of myocardial damage and atypical thrombosis. Despite the favorable and self-limiting clinical course of post-vaccinal myocarditis, in these cases a tight follow-up is advisable and vaccine adverse event reporting remains mandatory, especially if not described during pivotal clinical trials.

Additional prognostic value of heart rate reserve over left ventricular contractile reserve and coronary flow velocity reserve in diabetic patients with negative vasodilator stress echocardiography by regional wall motion criteria.

AIMS: In diabetic patients, a blunted left ventricular contractile reserve (LVCR) and/or a reduced coronary flow velocity reserve (CFVR) identify patients at higher risk in spite of stress echocardiography (SE) negative for ischaemia. Cardiac autonomic dysfunction contributes to risk profile independently of inducible ischaemia and can be assessed with heart rate reserve (HRR). We sought to assess the added prognostic value of HRR to LVCR and CFVR in diabetic patients with non-ischaemic SE. METHODS AND RESULTS: Six-hundred and thirty-six diabetic patients (age 68 ± 9 years, 396 men, ejection fraction 58 ± 10%) with sinus rhythm on resting electrocardiogram underwent dipyridamole SE in a two-centre prospective study with assessment of wall motion, force-based LVCR (stress/rest ratio, normal value > 1.1), CFVR of the left anterior descending coronary artery (stress/rest ratio, normal value >2.0), and HRR (stress/rest ratio, normal value >1.22). All-cause death was the only considered endpoint. During a median follow-up of 39 months, 94 (15%) patients died. Independent predictors of death were abnormal CFVR [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.0-2.52, P = 0.05], reduced LVCR (HR 1.76, 95% CI 1.15-2.69, P = 0.009), and blunted HRR (HR 1.92, 95% CI 1.24-2.96, P = 0.003). Eight-year death rate was 9% for patients with triple negativity (n = 252; 40%), 18% for those with single positivity (n = 216; 34%), 36% with double positivity (n = 124; 19%), and 64% for triple positivity (n = 44; 7%) (P < 0.0001). CONCLUSION: Diabetic patients with dipyridamole SE negative for ischaemia still may have a significant risk in presence of an abnormal LVCR and/or CFVR and/or HRR, which assess the underlying myocardial, microvascular, and cardiac autonomic dysfunction. CLINICAL TRIALS: Gov Identifier NCT 030.49995.

Machine Learning Algorithms for Prediction of Survival by Stress Echocardiography in Chronic Coronary Syndromes.

Stress echocardiography (SE) is based on regional wall motion abnormalities and coronary flow velocity reserve (CFVR). Their independent prognostic capabilities could be better studied with a machine learning (ML) approach. The study aims to assess the SE outcome data by conducting an analysis with an ML approach. We included 6881 prospectively recruited and retrospectively analyzed patients with suspected (n = 4279) or known (n = 2602) coronary artery disease submitted to clinically driven dipyridamole SE. The outcome measure was all-cause death. A random forest survival model was implemented to model the survival function according to the patient's characteristics; 1002 patients recruited by a single, independent center formed the external validation cohort. During a median follow-up of 3.4 years (IQR 1.6−7.5), 814 (12%) patients died. The mortality risk was higher for patients aged >60 years, with a resting ejection fraction < 60%, resting WMSI, positive stress-rest WMSI scores, and CFVR < 3.The C-index performance was 0.79 in the internal and 0.81 in the external validation data set. Survival functions for individual patients were easily obtained with an open access web app. An ML approach can be fruitfully applied to outcome data obtained with SE. Survival showed a constantly increasing relationship with a CFVR < 3.0 and stress-rest wall motion score index > Since processing is largely automated, this approach can be easily scaled to larger and more comprehensive data sets to further refine stratification, guide therapy and be ultimately adopted as an open-source online decision tool.

Prognostic Value of Heart Rate Reserve during Dipyridamole Stress Echocardiography in Patients With Abnormal Chronotropic Response to Exercise.

Heart rate reserve (HRR) during physical or pharmacological stress is a sign of cardiac autonomic function and sympathetic reserve, but it can be reduced during exercise for confounders such as poor motivation, drugs or physical fitness. In this study we sought to assess the prognostic meaning of HRR during dipyridamole stress echocardiography (DSE) in patients with abnormal chronotropic response to exercise. From 2004 to 2019, we prospectively acquired and retrospectively analyzed 379 patients (age 62 ± 11 years; ejection fraction 60 ± 5%) with suspected (n = 243) or known (n = 136) chronic coronary syndromes, referred to DSE for chronotropic incompetence during upright bicycle exercise-electrocardiography test defined as HRR used [(peak HR - rest HR) / (220 - age) - rest HR] ≤80% in patients off and ≤62% in patients on beta-blockers. All patients were in sinus rhythm and underwent DSE (0.84 mg/kg) within 3 months of exercise testing. During DSE, age-independent HRR (peak/rest HR) ≤1.22 was considered abnormal. All patients were followed-up. All-cause death was the only outcome measure. HRR during DSE was normal in 275 (73%) and abnormal in 104 patients (27%). During a follow-up of 9.0 ± 4.2 years, 67 patients (18%) died. The 15-year mortality rate was 23% in patients with normal and 61% in patients with abnormal HRR (p < 0.0001). At multivariable analysis a blunted HRR during DSE was an independent predictor of outcome (hazard ratio 2.01, 95% confidence intervals 1.23-3.29; p = 0.005) with age and diabetes, while neither inducible ischemia nor ongoing beta-blocker therapy were significant predictors. In conclusion, a blunted HRR during DSE predicts a worse survival in patients with chronotropic incompetence during exercise test. HRR during DSE is an appealingly simple biomarker of cardiac autonomic dysfunction independent of imaging, exercise and beta-blocker therapy.

Reduced Sympathetic Reserve Detectable by Heart Rate Response after Dipyridamole in Anginal Patients with Normal Coronary Arteries.

Background. Patients with ischemia and normal coronary arteries (INOCA) may show abnormal cardiac sympathetic function, which could be unmasked as a reduced heart rate reserve (HRR) during dipyridamole stress echocardiography (SE). Objectives. To assess whether HRR during dipyridamole SE predicts outcome. Methods. Dipyridamole SE was performed in 292 patients with INOCA. HRR was measured as peak/rest heart rate and considered abnormal when ≤1.22 (≤1.17 in presence of permanent atrial fibrillation). All-cause death was the only endpoint. Results. HRR during SE was normal in 183 (63%) and abnormal in 109 patients (37%). During a follow-up of 10.4 ± 5.5 years, 89 patients (30%) died. The 15-year mortality rate was 27% in patients with normal and 54% in those with abnormal HRR (p < 0.0001). In a multivariable analysis, a blunted HRR during SE was an independent predictor of outcome (hazard ratio 1.86, 95% confidence intervals 1.20-2.88; p = 0.006) outperforming inducible ischemia. Conclusions. A blunted HRR during dipyridamole SE predicts a worse survival in INOCA patients, independent of inducible ischemia.

Prognostic value of heart rate reserve is additive to coronary flow velocity reserve during dipyridamole stress echocardiography.

BACKGROUND: During dipyridamole stress echocardiography (SE), a blunted heart rate reserve (HRR) is a prognostically unfavourable sign of cardiac autonomic dysfunction. AIM: To assess the prognostic meaning of HRR and coronary flow velocity reserve (CFVR). METHODS: The study group comprised 2149 patients (1236 men; mean age 66±12 years) with suspected (n=1280) or known (n=869) coronary artery disease and without inducible regional wall motion abnormalities (RWMA) during dipyridamole SE (0.84mg/kg in 6min). We assessed CFVR of the left anterior descending artery with pulsed-wave Doppler as the ratio between hyperaemic peak and basal peak diastolic flow velocities (abnormal value≤2.0). HRR was calculated as the peak/resting ratio of heart rate from a 12-lead electrocardiogram (abnormal value≤1.22). All patients were followed up. RESULTS: CFVR and HRR were abnormal in 520 (24%) and 670 (31%) patients, respectively. There was a positive linear correlation between CFVR and HRR (r=0.30; P<0.0001). During a median follow-up of 22 months (1st quartile 12 months, 3rd quartile 35 months), 75 (6%) patients died. The annual mortality was 1.6% in the overall population, 0.5% in the 1224 (57%) patients with normal CFVR and HRR, 1.7% in the 405 (19%) patients with abnormal HRR only, 3.6% in the 255 (12%) patients with abnormal CFVR only, and 6.2% in the 265 (12%) patients with abnormal CFVR and HRR. CONCLUSIONS: HRR is weakly related to CFVR, and a blunted HRR usefully complements RWMA and CFVR for prediction of outcome with dipyridamole SE. The patient without inducible RWMA is still at intermediate risk, but the risk is low with concomitant preserved CFVR, and very low with concomitant normal HRR.

Prognostic Value of Heart Rate Reserve in Patients with Permanent Atrial Fibrillation during Dipyridamole Stress Echocardiography.

In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR ≤1.17 as the best predictor of mortality. At multivariable analysis, HRR ≤1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF.

Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications.

Secondary or functional mitral regurgitation (FMR) represents an increasing feature of mitral valve disease characterized by abnormal function of anatomically normal leaflets in the context of the impaired function of remodelled left ventricles. The anatomic and pathophysiological basis of FMR are briefly analyzed; in addition, the role of exercise echocardiography for the assessment of FMR is discussed in view of its relevance to clinical practice.

Drop-off in positivity rate of stress echocardiography based on regional wall motion abnormalities over the last three decades.

Previous studies have suggested a decline in positivity of stress cardiac imaging based on regional wall motion abnormalities (RWMA). To assess the rate of RWMA positivity of stress echocardiography (SE) over 3 decades in the same primary care SE lab. We retrospectively assessed the rate of SE positivity in 7626 SE tests (dipyridamole in 5053, dobutamine in 2496, exercise in 77) in consecutive patients with known or suspected coronary artery disease and /or heart failure who performed SE in a primary care referral center from April 1991 to May 2018. Starting April 2005, SE based on RWMA was complemented by assessment of coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery. Starting October 2016, we added left ventricular contractile reserve (LVCR). Starting October 2016, we also added B-lines by lung ultrasound. There was a progressive decline over time in the rate of SE positivity based on RWMA from 24% (1991-1999) to 10% (2000-2009) down to 4% (2010-2018) (p < 0.0001). Positivity rate was 29% with CFVR, 16% with LVCR, and 12% with B-lines. Over three decades, we observed a dramatic decline in SE positivity rate based on classical RWMA. In the last decade, the positivity rate rose sharply thanks to the stepwise introduction of CFVR, LVCR and B-lines as additional positivity criteria in integrated quadruple SE.