Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients ≥60 years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the United States (or 1.5 million people), the phenotypic penetrance is not known. Methods and Results The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) study is a currently accruing prospective multisite study designed to determine the prevalence of ATTR-CM using technetium-99m-pyrophosphate imaging in older (≥60 years of age) self-identified Black and Hispanic individuals with HF. Calculations of the penetrance and prevalence of the V122I allele, along with analyses of functional, biochemical, and echocardiographic parameters, were performed for the first 278 Black participants in SCAN-MP. The prevalence of ATTR-CM was 6.8% (95% CI, 4.2-10.5; n=19 cases), of whom 63% were ATTR wild-type. The prevalence of V122I was 6.5% (n=18 carriers), of whom 7 had ATTR-CM, yielding a phenotypic penetrance of 39% (95% CI, 17-64). V122I carriers with ATTR-CM evidenced more advanced HF than carriers without ATTR-CM. Prealbumin concentration was lowest among V122I carriers with ATTR-CM (12.9 mg/dL) versus carriers without ATTR-CM (21.0 mg/dL) and HF controls (25.0 mg/dL, P<0.0001). Conclusions Among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR-CM, 63% had wild-type, and of those with V122I, the phenotypic penetrance of ATTR-CM was 39% (95% CI, 17-64), suggesting that genotype alone is insufficient for diagnosis. Prealbumin concentration may be useful to identify V122I carriers with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.

Physical Performance in Black and Hispanic Outpatients With Heart Failure: The SCAN-MP Study.

Background: Deficits of physical function are associated with poor quality of life and adverse health outcomes, but data informing the association of these assessments among Black and Hispanic outpatients with heart failure (HF) are limited. Methods: The multicentre, prospective Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations (SCAN-MP) study identified Black and Hispanic subjects with stable HF, collected baseline characteristics, and took measures using the short physical performance battery. Subjects completed a Kansas City Cardiomyopathy Questionnaire (KCCQ), and the clinical outcomes of HF hospitalization and death were ascertained by telephone and review of the electronic health record. Results: Of 320 participants, 227 (70.9%) had physical deficits, defined by a battery score of ≤ 9. Patients with severe physical deficits reported overall lower KCCQ scores compared to those with no deficits (KCCQ score of 57.0 vs 72.4, P < 0.001). Physical limitation was significantly associated with risk of HF hospitalization, after adjustments for age, sex, and New York Heart Association class (severe physical deficit hazard ratio, 3.61; 95% confidence interval [CI], 1.19-10.93; P = 0.024; mild physical deficit hazard ratio, 2.59; 95% CI, 0.86-7.75; P = 0.090). Conclusions: Reduced physical performance is highly prevalent among Black and Hispanic outpatients with HF, and it is associated with overall KCCQ score, as well as an increased risk for HF hospitalization.

Contexte: La limitation physique est associée à une détérioration de la qualité de vie et à une aggravation de l'état de santé, mais il y a peu de données sur la corrélation entre ces paramètres chez les patients externes noirs et hispaniques atteints d'insuffisance cardiaque. Méthodologie: Dans l'étude multicentrique et prospective de dépistage de l'amylose cardiaque chez les populations minoritaires (SCAN-MP), on a ciblé des sujets noirs et hispaniques atteints d'insuffisance cardiaque stable, recueilli les caractéristiques initiales et mesuré les capacités au moyen du court test d'évaluation de la performance physique (short physical performance battery [SPPB]). Les sujets ont répondu au questionnaire de cardiomyopathie de Kansas City (KCCQ), et les critères cliniques des hospitalisations et des décès liés à l'insuffisance cardiaque ont été évalués par téléphone et par examen des dossiers de santé électroniques. Résultats: Des 320 participants, 227 (70,9 %) avaient des déficits physiques, définis par un score au SPPB de 9 ou moins. Les patients ayant des déficits physiques graves ont obtenu des scores globaux au KCCQ inférieurs aux patients sans déficit (score KCCQ de 57,0 contre 72,4; p < 0,001). La limitation physique est fortement associée au risque d'hospitalisation liée à l'insuffisance cardiaque, après ajustement pour tenir compte de l'âge, du sexe et de la classe d'insuffisance cardiaque de la New York Heart Association (rapport des risques instantanés [RRI] du déficit physique grave : 3,61; intervalle de confiance [IC] à 95 % de 1,19 à 10,93; p = 0,024; RRI du déficit physique léger : 2,59; IC à 95 % de 0,86 à 7,75; p = 0,090). Conclusions: La diminution de la performance physique est très fréquente chez les patients externes noirs et hispaniques atteints d'insuffisance cardiaque, et elle est corrélée au score global au KCCQ ainsi qu'à une augmentation du risque d'hospitalisation liée à l'insuffisance cardiaque.

Design and Rationale the SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an important cause of heart failure in older individuals. Misfolding and deposition of transthyretin or prealbumin protein causes ATTR-CM in the context of a normal (wild-type) or variant TTR sequence. Variant ATTR-CM is most commonly caused by the substitution of valine for isoleucine at position 122 in transthyretin (Val122Ile or pV142I, almost exclusively observed in individuals of West African ancestry), demonstrated in 3.4% of self-identified Black individuals in the United States with an estimated 1.5 million carriers. Despite the large number of known pV142I carriers, the proportion of older Black patients with heart failure attributable to ATTR-CM remains unknown. Methods To address this knowledge gap, the SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations) study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL139671) to enroll a targeted population of self-identified, community-dwelling Black or Caribbean Hispanic patients (many of whom are of West African ancestry) >60 years of age with heart failure and identify ATTR-CM by noninvasive nuclear imaging. The principal objective of SCAN-MP is to determine the prevalence of ATTR-CM in this population. Secondary objectives will explore TTR genotype, demographics, progression of variant versus wild-type ATTR-CM, and biochemical mechanisms of transthyretin amyloid fibril formation. Conclusions The SCAN-MP study is the largest, prospective study of cardiac amyloidosis in Black and Hispanic individuals. Both wild-type and variant ATTR-CM are now treatable with the US Food and Drug-approved drug tafamidis. The insights gained from SCAN-MP are likely to improve those at risk for or afflicted with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.

Diagnostic performance characteristics of planar quantitative and semi-quantitative parameters of Tc99m pyrophosphate (PYP) imaging for diagnosis of transthyretin (ATTR) cardiac amyloidosis: the SCAN-MP study.

BACKGROUND: The optimal heart-to-contralateral chest (H/CL) ratio threshold for non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) using Tc99m pyrophosphate (PYP) imaging in a population with low pretest probability is not known. METHODS: Using myocardial PYP retention by SPECT as the reference standard, we evaluated the diagnostic performance of different semi-quantitative and quantitative (H/CL chest ratio) planar parameters obtained from 3-hour PYP imaging in a prospectively recruited cohort of minority older adults with heart failure and increased LV wall thickness. RESULTS: Of 229 patients, 14 were found to have ATTR-CA (6.1%). No PYP uptake (grade 0) was observed in 77% of scans, all grade 3 scans were ATTR-CA, and only 4 of 11 (36%) grade 2 scans were ATTR-CA. An H/CL threshold of ≥ 1.4 maximized specificity (99%) and positive predictive value (93%) but resulted in decreased sensitivity (93%), compared to the ≥ 1.3 threshold which had 100% sensitivity. CONCLUSION: Among patients with a low pretest likelihood of ATTR-CA, planar interpretation, while useful to exclude disease, must be interpreted with caution. H/CL ratio threshold of ≥ 1.3 resulted in clinically important misclassifications. These data suggest that quantitative planar imaging thresholds may not be appropriate to apply in low pretest likelihood populations being evaluated for ATTR-CA.

Relation of Body Mass Index to Transthyretin Cardiac Amyloidosis Particularly in Black and Hispanic Patients (from the SCAN-MP Study).

Heart failure with preserved ejection fraction is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing heart failure with preserved ejection fraction caused by transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatment. We analyzed a single-center retrospective cohort to determine the association of body mass index (BMI) with a composite of either ATTR-CA or the valine-to-isoleucine substitution (Val122Ile) variant genotype (ATTR-CA+Val122Ile). These BMI differences were prospectively evaluated in the multicenter Screening for Cardiac Amyloidosis using nuclear imaging for Minority Populations (SCAN-MP) study of Black and Hispanic patients with heart failure. The association of BMI with ATTR-CA+Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, gender, and maximum left ventricle wall thickness in multivariable logistic regression. In the retrospective analysis (n = 469), ATTR-CA+Val122Ile was identified in n = 198 (40%), who had a lower median BMI (25.8 kg/m2, interquartile range [IQR] 23.4 to 28.9) than other patients (27.1 kg/m2, IQR 23.9 to 32.0) (p <0.001). In multivariable logistic regression, BMI <30 kg/m2 (odds ratio 2.6, 95% confidence interval 1.5 to 4.5) remained independently associated with ATTR-CA+Val122Ile with a greater association in Black and Hispanic patients (odds ratio 5.8, 95% confidence interval 1.7 to 19.6). In SCAN-MP (n = 201), 17 (8%) had either ATTR-CA (n = 10) or were Val122Ile carriers (n = 7) with negative pyrophosphate scans. BMI was lower (25.4 kg/m2 [IQR 24.3 to 28.2]) in ATTR-CA+Val122Ile patients than in non-amyloid patients (32.7 kg/m2 [28.3 to 38.6]) (p <0.001), a finding that persisted in multivariable analysis (p = 0.002). In conclusion, lower BMI is associated with ATTR-CA+Val122Ile in heart failure with increased left ventricle wall thickness, particularly in Black and Hispanic patients, and may aid in the identification of those benefiting from ATTR-CA evaluation.

A curious case of Lyme carditis in an urban hospital.

Lyme carditis (LC), a manifestation of early disseminated Lyme disease, most commonly presents with cardiac conduction abnormalities. It is a transient condition with good prognosis but in extremely rare cases may be life-threatening. We describe a 42-year-old man who presented with progressively worsening generalized weakness, presyncope and dyspnea on exertion for 2 weeks after sustaining a tick bite. He subsequently developed a 'bull's eye rash' on his flank 2 days before his presentation. He was found to have symptomatic third-degree AV conduction blockade with a ventricular escape rhythm resulting in a brief cardiac arrest. Intravenous (IV) ceftriaxone was commenced empirically and a temporary transvenous pacemaker was placed. In a few days he showed dramatic, rapid improvement; the pacemaker was removed, and the patient was discharged on oral doxycycline to complete a 24-day course. This case is unique due to its occurrence in an urban hospital where such cases are uncommon. Cardiac arrest, although brief in this case, is a rare occurrence. Lyme carditis was a surprise diagnosis in our hospital due to the patient's geographical dislocation during the COVID-19 pandemic.

A Case of Right Ventricular Dysfunction with Right Ventricular Failure Secondary to Obesity Hypoventilation Syndrome.

BACKGROUND Obesity hypoventilation syndrome (OHS) is characterized by a body mass index (BMI) ≥30 kg/m², daytime hypercapnia, an arterial carbon dioxide tension ≥45 mmHg, and obstructive sleep apnea (OSA). OHS can lead to pulmonary hypertension. It has not been clearly demonstrated that OHS with pulmonary hypertension can lead to right ventricular dysfunction and right heart failure. A case is presented of right ventricular dysfunction and right ventricular failure secondary to OHS. CASE REPORT A 53-year-old man, who was morbidly obese with a BMI of 75 kg/m², presented with shortness of breath (SOB) and hypercapnia. He had never smoked but had a history of severe OSA and hypertension. On examination, the patient was obese with normal lung auscultation and mild pitting edema of the lower extremities. A spiral computed tomography (CT) angiogram showed no evidence of pulmonary embolism or interstitial lung disease. Pulmonary function testing showed no obstructive airway disease and a normal diffusion capacity. Two-dimensional transthoracic echocardiogram (TTE) showed normal left ventricular function and a dilated right ventricle (RV) with a flattened septal wall, moderate tricuspid regurgitation, and an estimated right ventricular systolic pressure of 55-60 mmHg. The patient was discharged on continuous positive airway pressure (CPAP) and oxygen at night, and as needed during the day. CONCLUSIONS This report has shown that OHS without underlying causes of alveolar hypoventilation can result in isolated right ventricular dysfunction and right ventricular failure.

Saddle Pulmonary Embolism with Thrombus in Transit across a Patent Foramen Ovale.

This is the case of a 25-year-old obese man who presented with acute shortness of breath, chest pain, and palpitations. Of note, he lives a sedentary lifestyle and was recently hospitalized for incision and drainage of a left foot abscess. On presentation he was tachypnoeic, tachycardiac, and hypoxic but blood pressure was stable. Laboratory studies were significant for elevated D-dimer and mildly increased troponin. On further investigation he was found to have a saddle pulmonary embolism with massive clot burden. Echocardiogram revealed thrombus in transit and McConnell's sign. He underwent surgical embolectomy and closure of a patent foramen ovale. This is a particularly rare case, especially in such a young patient. Because this is a rare diagnosis, with insufficient data, there is no formally established treatment guideline. However, in patients who are good surgical candidates, studies have shown better outcome with surgical embolectomy as compared to anticoagulation alone or thrombolysis.

The optimal duration of dual antiplatelet therapy in patients receiving percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) following drugeluting stent (DES) implantation remains a subject of an ongoing debate. METHODS: MEDLINE, EMBASE, Scopus and CENTRAL databases were searched for eligible randomized controlled trials (RCTs) that compared short-term (ï¿¡ 6 months) DAPT with long-term (≥ 12 months) DAPT following DES implantation. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR), stroke, or major bleeding. The secondary outcome were the individual components of the primary outcome, cardiovascular death, stent thrombosis and any bleeding episode. RESULTS: A total of 15,378 patients from 7 RCTs were studied. There were no statistically significant differences between the short-term and long-term DAPT groups with respect to the occurrence of the primary outcome (risk ratio [RR] 1.017; 0.872-1.186; I2 = 0%), all cause death (RR 0.896; 0.708-1.134), cardiovascular death (RR 0.924; 0.668-1.279), MI (RR 1.139; 0.887-1.461), TVR (RR 1.174; 0.916-1.505), stent thrombosis (RR 1.264; 0.786-2.032), and stroke (RR 0.876; 0.685-1.611). However, there was a statistically significant lower risk of major bleeding in the short-term DAPT group (RR 0.57; 0.36-0.90; p = 0.02). There were no statistically significant differences in the sub-group analysis of patients with diabetes and patients presenting with acute coronary syndrome, RR 1.029; 0.745-1.421 and RR 1.062; 0.785-1.438, respectively. CONCLUSIONS: There was no difference in efficacy outcomes between short-term and long-term DAPT following DES, even among high-risk patients. However, longer duration of DAPT was found to be associated with increased risk of major bleeding.

Coronary artery spasm: An often overlooked diagnosis.

Coronary vasospasm can lead to myocardial injury and even sudden cardiac death. It has generally been overlooked as a diagnosis since atherosclerosis is a more common cause of acute coronary syndromes and because of the dilemma involved in its diagnosis. A middle-aged man with a history of smoking and cocaine use presented to the emergency department with left-sided arm/chest discomfort and diaphoresis. The electrocardiogram showed anterior ST elevation and hyper-acute T waves, which completely resolved shortly after sublingual nitroglycerin was administered. Subsequent angiogram revealed a 70% focal stenosis in the mid-left anterior descending artery. Coronary vasospasm occurs more commonly in arteries with underlying atheromatous disease, although normal vessels are not excluded. Cigarette smoking and cocaine use are among the major culprits that have been implicated as risk factors for the occurrence of coronary vasospasm. Eventually, the patient had percutaneous coronary intervention of his left-anterior descending artery and remained asymptomatic.

Safety and efficacy of transradial aortoiliac interventions.

BACKGROUND: This study compares transradial approach (TRA) aortoiliac angioplasty/stenting to the transfemoral approach (TFA). METHODS: We reviewed our peripheral database for aortoiliac interventions performed between 2007 and 2009. Demographics, clinical characteristics, procedural, and lesion details were collected. The efficacy endpoints included procedural success, ankle-brachial index (ABI) improvement, and time to discharge. The safety endpoints were as follows: occurrence of intra-/periprocedural complications, 30-day MACE, and access-site complications (minor/major). The subjects were divided into two groups, TRA and TFA, and compared using appropriate statistics. RESULTS: Twenty-seven patients had 33 lesions treated via TRA, and 41 patients had 47 lesions treated via TFA access. Baseline demographic differences between the TRA and TFA groups were similar, including mean Rutherford category (2.9 vs. 2.6, P = 0.31) and preintervention ABI (0.64 vs. 0.67, P = 0.80). There was a significantly higher percentage of total occlusions in the TRA group (27.3 vs. 8.5%, P = 0.03). Dye use (238 vs. 213 mL, P = 0.35) and fluoroscopy time (30 vs. 27 min, P = 0.60) were similar. Procedural success rate was similar (87.9 vs. 97.8%, P = 0.15), as well as the improvement in mean ABI (TRA: 0.64-0.77 and TFA: 0.67-0.85, P = 0.77). The time to discharge was significantly shorter for the TRA group (14.4 vs. 20.9 hr, P = 0.003). There were no 30-day MACE or major access-site complications, but minor access-site complications were lower in the TRA group (0.0 vs. 7.3%, P = 0.28), although nonsignificant. CONCLUSIONS: The TRA to aortoiliac interventions is as safe and effective as the TFA with the advantage of a lower rate of access-site complications and shorter hospitalization time.

Transradial peripheral vascular interventions.

Recently the importance of post procedure bleeding contributing to both short-term and long-term mortality has lead to a renewed interest in transradial coronary interventions in the United States. It has been long known that the incidence of access site bleeding is dramatically decreased by transradial access but the procedure is only used in 1% of coronary interventions in the United States, far below the rest of the world. In India, Japan and some European centers 50% of interventions are transradial. To extend this benefit of lower incidence of access site complications, we started using a transradial approach for peripheral interventions for the lower extremities, renal and subclavian arteries. By experience, we realized that in many cases the radial approach makes the procedure actually simpler. Also, in many instances, the transradial approach allows discharge of the patient on the same day. In this paper, we describe our approach to lower extremity, renal and subclavian interventional procedures.

Transradial intervention of iliac and superficial femoral artery disease is feasible.

BACKGROUND: Percutaneous intervention of iliac artery (IA) and superficial femoral artery (SFA) disease is often performed via ipsilateral or contralateral femoral access. However, this approach may be difficult in patients with severe iliac or common femoral artery atherosclerosis, morbid obesity, or conditions prohibiting prolonged bed rest. Percutaneous transradial coronary intervention has gained popularity due to the low frequency of access site complications, early ambulation, and perhaps cost savings with early discharge. Transradial intervention (TRI) of IA and SFA disease has been previously described only in anecdotal case reports. METHODS: Out of 159 patients who underwent IA and SFA intervention, 15 had their intervention attempted via the radial artery. TRI was attempted at the operator's discretion for one of the following reasons: absent femoral pulses, severe bilateral IA disease, obesity, or conditions prohibiting prolonged supine rest. Clinical and procedural characteristics were collected retrospectively. RESULTS: Fourteen patients (93%) had successful intervention completed through the transradial approach. One patient needing an intervention of the distal SFA was converted to contralateral femoral approach because of the inadequate stent shaft length. Eighteen IA lesions and six SFA lesions were treated successfully with a good final angiographic result via a 6 FR radial access system. The ankle brachial index improved from a mean of 0.66 to 0.93. None of the patients had any procedural or access site-related complications. CONCLUSIONS: TRI is a feasible and safe alternative for percutaneous treatment of IA and SFA disease in carefully selected patients.

Transradial bilateral iliac stenting.

Bilateral stenting of the common iliac arteries via the radial access route, in the same setting, is presented in this case report. Radial access limits bleeding complications, avoids the crossover technique and allows same-day discharge.

Nesiritide in pulmonary hypertension.

We present the case of a patient with severe symptomatic pulmonary hypertension due to rheumatic mitral valve disease who was refractory to traditional therapies, including prostacyclin. Therapy with continuous nesiritide infusion resulted in significant and sustained decreases in pulmonary vascular resistance, an improvement in renal function, and the maintenance of euvolemia.

Frequency of and outcome of acute coronary syndromes in patients with human immunodeficiency virus infection.

Fifty-one patients with human immunodeficiency virus infection and acute coronary syndromes were identified. Nearly all patients (98%) had traditional coronary risk factors. Revascularization procedures were performed safely with low in-hospital mortality.