Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized. Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening. Design, Setting, and Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort). Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis. Main Outcomes and Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex. Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002). Conclusions and Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Characterization of Aerosol Generation During Various Intensities of Exercise.

BACKGROUND: Characterization of aerosol generation during exercise can inform the development of safety recommendations in the face of COVID-19. RESEARCH QUESTION: Does exercise at various intensities produce aerosols in significant quantities? STUDY DESIGN AND METHODS: In this experimental study, subjects were eight healthy volunteers (six men, two women) who were 20 to 63 years old. The 20-minute test protocol of 5 minutes rest, four 3-minute stages of exercise at 25%, 50%, 75%, and 100% of age-predicted heart rate reserve, and 3 minutes active recovery was performed in a clean, controlled environment. Aerosols were measured by four particle counters that were place to surround the subject. RESULTS: Age averaged 41 ± 14 years. Peak heart rate was 173 ± 17 beat/min (97% predicted); peak maximal oxygen uptake was 33.9 ± 7.5 mL/kg/min; and peak respiratory exchange ratio was 1.22 ± 0.10. Maximal ventilation averaged 120 ± 23 L/min, while cumulative ventilation reached 990 ± 192 L. Concentrations increased exponentially from start to 20 minutes (geometric mean ± geometric SD particles/liter): Fluke >0.3 µm = 66 ± 1.8 → 1605 ± 3.8; 0.3-1.0 µm = 35 ± 2.2 → 1095 ± 4.6; Fluke 1.0-5.0 µm = 21 ± 2.0 → 358 ± 2.3; P-Trak anterior = 637 ± 2.3 → 5148 ± 3.0; P-Trak side = 708 ± 2.7 → 6844 ± 2.7; P-Track back = 519 ± 3.1 → 5853 ± 2.8. All increases were significant at a probability value of <.05. Exercise at or above 50% of predicted heart rate reserve showed statistically significant increases in aerosol concentration. INTERPRETATION: Our data suggest exercise testing is an aerosol-generating procedure and, by extension, other activities that involve exercise intensities at or above 50% of predicted heart rate reserve. Results can guide recommendations for safety of exercise testing and other indoor exercise activities.

Mitigation of Aerosols Generated During Exercise Testing With a Portable High-Efficiency Particulate Air Filter With Fume Hood.

BACKGROUND: The role of portable high-efficiency particulate air (HEPA) filters for supplemental aerosol mitigation during exercise testing is unknown and might be relevant during COVID-19 pandemic. RESEARCH QUESTION: What is the effect of portable HEPA filtering on aerosol concentration during exercise testing and its efficiency in reducing room clearance time in a clinical exercise testing laboratory? STUDY DESIGN AND METHODS: Subjects were six healthy volunteers aged 20 to 56 years. In the first experiment, exercise was performed in a small tent with controlled airflow with the use of a stationary cycle, portable HEPA filter with fume hood, and particle counter to document aerosol concentration. Subjects performed a four-stage maximal exercise test that lasted 12 min plus 5 min of pretest quiet breathing and 3 min of active recovery. First, they exercised without mitigation then with portable HEPA filter running. In a separate experiment, room aerosol clearance time was measured in a clinical exercise testing laboratory by filling it with artificially generated aerosols and measuring time to 99.9% aerosol clearance with heating, ventilation, and air conditioning (HVAC) only or HVAC plus portable HEPA filter running. RESULTS: In the exercise experiment, particle concentrations reached 1,722 ± 1,484/L vs 96 ± 124/L (P < .04) for all particles (>0.3 µm), 1,339 ± 1,281/L vs 76 ± 104/L (P < .05) for smaller particles (0.3 to 1.0 µm), and 333 ± 209/L vs 17 ± 19/L (P < .01) for larger particles (1.0 to 5.0 µm) at the end of the protocol in a comparison of mitigation vs portable HEPA filter. Use of a portable HEPA filter in a clinical exercise laboratory clearance experiment reduced aerosol clearance time 47% vs HVAC alone. INTERPRETATION: The portable HEPA filter reduced the concentration of aerosols generated during exercise testing by 96% ± 2% for all particle sizes and reduced aerosol room clearance time in clinical exercise testing laboratories. Portable HEPA filters therefore might be useful in clinical exercise testing laboratories to reduce the risk of COVID-19 transmission.

Stress Testing in the Evaluation of Stable Chest Pain in a Community Population.

OBJECTIVE: To evaluate the use of stress testing in a community population with de novo stable chest pain, a normal resting electrocardiogram (ECG), and the ability to exercise. PATIENTS AND METHODS: We identified eligible patients by searching the electronic medical record of all outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013. We determined the frequency of initial exercise stress testing, computed tomography coronary angiography, and invasive coronary angiography, as well as the use of subsequent second procedures (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting) within 90 days. Patients were followed for 5 years for death, nonfatal myocardial infarction, and hospitalization for unstable angina. RESULTS: The data search identified 1175 patients with chest pain and normal resting ECGs. Only 331 patients underwent cardiac testing. A slight majority (185; 55.9%) underwent an exercise ECG alone. The remainder underwent exercise echocardiography (112; 33.8%), exercise single-photon-emission computed tomography (32; 9.7%), or computed tomography coronary angiography (2; 0.9%). Few patients (30; 9.1%) required additional testing within 90 days. Of the 14 patients (4.2%) who underwent invasive coronary angiography, 12 (85.7%) had significant coronary artery disease, and were referred for percutaneous coronary intervention or coronary artery bypass grafting. At 5 years, the mortality rate was 1.2%, and the combined event rate was 3.8%. CONCLUSION: Most community patients with chest pain and a normal resting ECG do not require further cardiac evaluation. In patients who require testing, and are able to exercise, noninvasive stress testing is preferred. Invasive coronary angiography is applied selectively and associated with a high rate of significant coronary artery disease and referral to coronary revascularization. Long-term outcomes are excellent.

Temporal Trends of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Coronary Artery Disease: A 22-Year Experience From a Tertiary Academic Medical Center.

BACKGROUND: There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously. METHODS AND RESULTS: We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 (P<0.001). CONCLUSIONS: In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.

Handheld echocardiography during hospitalization for acute myocardial infarction.

BACKGROUND: Handheld echocardiography (HHE) is concordant with standard transthoracic echocardiography (TTE) in a variety of settings but has not been thoroughly compared to traditional TTE in patients with acute myocardial infarction (AMI). HYPOTHESIS: Completed by experienced operators, HHE provides accurate diagnostic capabilities compared with standard TTE in AMI patients. METHODS: This study prospectively enrolled patients admitted to the coronary care unit with AMI. Experienced sonographers performed HHE with a V-scan. All patients underwent clinical TTE. Each HHE was interpreted by 2 experts blinded to standard TTE. Agreement was assessed with κ statistics and concordance correlation coefficients. RESULTS: Analysis included 82 patients (mean age, 66 years; 74% male). On standard TTE, mean left ventricular (LV) ejection fraction was 46%. Correlation coefficients between HHE and TTE were 0.75 (95% confidence interval: 0.66 to 0.82) for LV ejection fraction and 0.69 (95% confidence interval: 0.58 to 0.77) for wall motion score index. The κ statistics ranged from 0.47 to 0.56 for LV enlargement, 0.55 to 0.79 for mitral regurgitation, and 0.44 to 0.57 for inferior vena cava dilatation. The κ statistics were highest for the anterior (0.81) and septal (0.71) apex and lowest for the mid inferolateral (0.36) and basal inferoseptal (0.36) walls. CONCLUSIONS: In patients with AMI, HHE and standard TTE demonstrate good correlation for LV function and wall motion. Agreement was less robust for structural abnormalities and specific wall segments. In experienced hands, HHE can provide a focused assessment of LV function in patients hospitalized with AMI; however, HHE should not substitute for comprehensive TTE.

Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing.

Temporal trends of single-photon emission computed tomography myocardial perfusion imaging in patients without prior coronary artery disease: A 22-year experience at a tertiary academic medical center.

BACKGROUND: Between 1990 and 2006, there was a large national increase in utilization of single-photon emission computed tomography myocardial perfusion imaging (SPECT) for assessment of coronary artery disease (CAD). We aim to examine the trends of SPECT test results and patients' characteristics at Mayo Clinic Rochester. METHODS: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between January 1, 1991, and December 31, 2012, in patients without prior CAD. The study cohort was divided into 5 time periods: 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2012. RESULTS: There were 35,894 eligible SPECT tests (mean age 62.5 ± 12 years, 54% men). Annual utilization of SPECT increased significantly in 1992-2002 but then decreased without evidence of test substitution with stress echocardiography. There were modest changes in CAD risk factors over time. Testing of asymptomatic patients doubled (21.9% in 1991-1995 to 40% in 2006-2010) but later decreased to 33.6% in 2011-2012. Tests on patients with typical angina decreased dramatically (18.3% in 1991-1995 to 6.7% in 2011-2012). Summed stress score, summed difference score, and high-risk SPECT tests all decreased over time in both symptomatic and asymptomatic patients regardless of stress modality (exercise vs pharmacologic). CONCLUSIONS: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased in 1992-2002 but then decreased. Despite similar CAD risk factors and decreased utilization after 2003, more tests were low risk; summed stress score, summed difference score, and high-risk tests all decreased. Our findings confirm previous observations that SPECT was increasingly used in patients with a lower prevalence of CAD.

Abnormal stress echocardiography findings in cardiac amyloidosis.

BACKGROUND: Cardiac involvement in immunoglobulin light chain (amyloid light chain, AL) amyloidosis is characterized by myocardial interstitial deposition but can also cause obstructive deposits in the coronary microvasculature. METHODS: We retrospectively identified 20 patients who underwent stress echocardiography within 1 year prior to the histologic diagnosis of AL amyloidosis. Only patients with cardiac amyloidosis and no known obstructive coronary disease were included. RESULTS: Stress echocardiograms (13 exercise; 7 dobutamine) were performed for evaluation of dyspnea and/or chest pain. Stress-induced wall motion abnormalities (WMAs) occurred in 11 patients (55%), 4 of whom had normal left ventricular wall thickness. Coronary angiogram was performed in 9 of 11 patients and demonstrated no or mild epicardial coronary artery disease. Seven (54%) patients had an abnormal exercise blood pressure which occurred with similar likelihood between those with and without stress-induced WMAs. CONCLUSIONS: Stress-induced WMAs and abnormal exercise blood pressure may occur in patients with cardiac AL amyloidosis despite the absence of significant epicardial coronary artery disease. This finding should raise the possibility of cardiac amyloidosis even in the absence of significant myocardial thickening.

Noninvasive Stress Testing for Coronary Artery Disease.

Stress testing remains the cornerstone for noninvasive assessment of patients with possible or known coronary artery disease (CAD). The most important application of stress testing is risk stratification. Most patients who present for evaluation of stable CAD are categorized as low risk by stress testing. These low-risk patients have favorable clinical outcomes and generally do not require coronary angiography. Standard exercise treadmill testing is the initial procedure of choice in patients with a normal or near-normal resting electrocardiogram who are capable of adequate exercise. Stress imaging is recommended for patients with prior revascularization, uninterpretable electrocardiograms, or inability to adequately exercise.

Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease.

BACKGROUND: Symptoms and survival of patients with carcinoid syndrome have improved, but development of carcinoid heart disease (CaHD) continues to decrease survival. OBJECTIVES: This study aimed to analyze patient outcomes after valve surgery for CaHD during a 27-year period at 1 institution to determine early and late outcomes and opportunities for improved patient care. METHODS: We retrospectively studied the short-term and long-term outcomes of all consecutive patients with CaHD who underwent valve replacement at our institution between 1985 and 2012. RESULTS: The records of 195 patients with CaHD were analyzed. Pre-operative New York Heart Association class was III or IV in 125 of 178 patients (70%). All had tricuspid valve replacement (159 bioprostheses, 36 mechanical), and 157 underwent a pulmonary valve operation. Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). There were 20 perioperative deaths (10%); after 2000, perioperative mortality was 6%. Survival rates (95% confidence intervals) at 1, 5, and 10 years were 69% (63% to 76%), 35% (28% to 43%), and 24% (18% to 32%), respectively. Overall mortality was associated with older age, cytotoxic chemotherapy, and tobacco use; 75% of survivors had symptomatic improvement at follow-up. Presymptomatic valve operation was not associated with late survival benefit. CONCLUSIONS: Operative mortality associated with valve replacement surgery for CaHD has decreased. Symptomatic and survival benefit is noted in most patients when CaHD is managed by an experienced multidisciplinary team.

Use of Echocardiography in Olmsted County Outpatients With Chest Pain and Normal Resting Electrocardiograms Seen at Mayo Clinic Rochester.

OBJECTIVE: To determine how often unnecessary resting echocardiograms that are "not recommended" by clinical practice guidelines are performed in patients with stable chest pain and normal resting electrocardiograms (ECGs). PATIENTS AND METHODS: We performed a retrospective search of electronic medical records of all outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013, to identify residents of Olmsted County, Minnesota, with stable chest pain and known or suspected coronary artery disease who underwent resting echocardiography and had normal resting ECGs and no other indication for echocardiography. RESULTS: Of the 8280 outpatients from Olmsted County who were evaluated at Mayo Clinic Rochester with chest pain, 590 (7.1%) had resting echocardiograms. Ninety-two of these 590 patients (15.6%) had normal resting ECGs. Thirty-three of these 92 patients (35.9%) had other indications for echocardiography. The remaining 59 patients (10.0% of all echocardiograms and 0.7% of all patients) had normal resting ECGs and no other indication for echocardiography. Fifty-seven of these 59 patients (96.6%) had normal echocardiograms. Thirteen of these 59 echocardiograms (22.0%) were "preordered" before the provider (physicians, nurses, physician assistants) visit. CONCLUSION: The overall rate of echocardiography in Olmsted County outpatients with chest pain seen at Mayo Clinic Rochester is low. Only 1 in 10 of these echocardiograms was performed in violation of the class III recommendation in the American College of Cardiology Foundation/American Heart Association guidelines for the management of stable angina. These unnecessary echocardiograms were almost always normal. The rate of unnecessary echocardiograms could be decreased by eliminating preordering.

Feasibility and diagnostic accuracy of exercise treadmill nitrogen-13 ammonia PET myocardial perfusion imaging of obese patients.

BACKGROUND: Treadmill exercise nitrogen-13 ((13)N)-ammonia positron emission tomography (PET) has logistical challenges and limited literature. We aimed to assess its feasibility, image quality, and diagnostic accuracy in obese and nonobese patients. METHODS AND RESULTS: Between 2009 and 2012, 10,804 patients were referred for myocardial perfusion imaging, including 300 for treadmill PET, of whom 265 were included in this study. Treadmill testing and PET were performed using standard procedures. Image quality, perfusion, and summed stress score (SSS) were assessed. Invasive coronary angiography was performed within 90 days of PET in 43 patients. Mean ± SD body mass index (BMI) was 35.7 ± 7.7 kg/m(2) (range 19.5-63.5 kg/m(2)). Feasibility of treadmill (13)N-ammonia PET was 100%. Exercise duration was less for obese patients than nonobese patients (P < .001). Image quality was rated good for 96.9% of obese and 100% of nonobese patients. For all patients, sensitivity was 86.4% and specificity was 74.4%. Diagnostic accuracy did not change significantly with increasing BMI. SSS remained significant in predicting angiographic coronary artery disease after adjustment for age, sex, and Duke treadmill score. CONCLUSIONS: Treadmill (13)N-ammonia PET is highly feasible, yields good image quality, and has moderately high diagnostic accuracy in a small subset of obese and nonobese patients who are deemed able to perform treadmill exercise.

Noninvasive stress testing for coronary artery disease.

Stress testing remains the cornerstone for noninvasive assessment of patients with possible or known coronary artery disease (CAD). The most important application of stress testing is risk stratification. Most patients who present for evaluation of stable CAD are categorized as low risk by stress testing. These low-risk patients have favorable clinical outcomes and generally do not require coronary angiography. Standard exercise treadmill testing is the initial procedure of choice in patients with a normal or near-normal resting electrocardiogram who are capable of adequate exercise. Stress imaging is recommended for patients with prior revascularization, uninterpretable electrocardiograms, or inability to adequately exercise.

Evaluation of apical subtype of hypertrophic cardiomyopathy using cardiac magnetic resonance imaging with gadolinium enhancement.

Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of HC. We sought to characterize cardiac magnetic resonance imaging (MRI) findings among apical HC patients. This was a retrospective review of consecutive patients with a diagnosis of apical HC who underwent cardiac MRI examinations at the Mayo Clinic (Rochester, MN) from August 1999 to October 2011. Clinical and demographic data at the time of cardiac MRI study were abstracted. Cardiac MRI study and 2-dimensional echocardiograms performed within 6 months of the cardiac MRI were reviewed; 96 patients with apical HC underwent cardiac MRI examinations. LV end-diastolic and end-systolic volumes were 130.7 ± 39.1 ml and 44.2 ± 20.9 ml, respectively. Maximum LV thickness was 19 ± 5 mm. Hypertrophy extended beyond the apex into other segments in 57 (59.4%) patients. Obstructive physiology was seen in 12 (12.5%) and was more common in the mixed apical phenotype than the pure apical (19.3 vs 2.6%, p = 0.02). Apical pouches were noted in 39 (40.6%) patients. Late gadolinium enhancement (LGE) was present in 70 (74.5%) patients. LGE was associated with severe symptoms and increased maximal LV wall thickness. In conclusion, cardiac MRI is well suited for studying the apical form of HC because of difficulty imaging the cardiac apex with standard echocardiography. Cardiac MRI is uniquely suited to delineate the presence or absence of an apical pouch and abnormal myocardial LGE that may have implications in the natural history of apical HM. In particular, the presence of abnormal LGE is associated with clinical symptoms and increased wall thickness.